Regulation of tissue regeneration and homeostasis through ON-OFFcontrol of the Met/HGF receptor

• Project/Area Number: 18570127
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kanazawa University (2007); Osaka University (2006)
• Principal Investigator: MATSUMOTO Kunio Kanazawa University, Cancer Research Insitute, 教授 (90201780)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Takahiro Kanazawa University, Cancer Research Institute, 助教 (70414018)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: HGF / Met / contact inhibition / tissue regeneration / knockout mouse / protein tyrosine phosnhatase / tyrosine kinase / growth factor

Research Abstract

HGF (hepatocyte growth factor) and Met/HGF receptor tyrosine kinase play important roles in tissue regeneration. In non-injured normal tissues, Met activation/tyrosine phosphorylation is suppressed even following binding with HGF. Thus, HGF-dependent Met receptor activation may be regulated by not only HGF-binding but also cellular context such as cell-cell contact and cellular injury. In this research, suppressive mechanisms of Met activation through cell-cell contact and Ser985 phosphorylation in the juxtamembrane domain of the Met were investigated.
1. In hepatocytes cultured at a sparse cell density, HGF induced prolonged Met activation and a marked mitogenic response. In contrast, HGF induced transient Met activation but failed to induce mitogenic response in confluent hepatocytes with tight cell-cell contact. Expression of the protein tyrosine phosphatase, LAR increased following HGF-stimulation specifically in confluent hepatocytes. LAR associated with Met and dephosphorylated ty rosine-phosphorylated Met. Thus functional association of LAR and Met underlies the inhibitory mechanism by which HGF-dependent Met activation is suppressed by cell-cell contact.
2. In hepatocytes in culture, HGF-dependent Met tyrosine phosphorylation/activation was inhibited when Ser985 was phosphorylated. In the normal liver, Met Ser985 was phosphorylated, however, Ser985 was dephosphorylated after hepatic injury such as partial hepatectomy. In reciprocal manner to Ser985 phosphorylation, Met was activated after hepatic injury. The results suggest that Ser985 in the juxtamembrane domain of Met is regulated by tissue injury and that Ser985 phosphorylation in the juxtamembrane domain of Met may be a mechanism by which HGF-dependent Met activation is suppressed in non-injured organs. Because Met receptor deleted with the juxtamembrane is naturally expressed as a splicing variant, the juxtamembrane of the Met may play an important role in regulation of HGF-dependent Met activation in response to tissue injury.
3. Physiological significance of the juxtamembrane domain of Met in the development and tissue regeneration is investigated using the transgenic mice which express only variant Met deleted with the juxtamembrane domain.

Research Products

• [Journal Article] Generation of engineered recombinant hepatocyte growth factor cleaved and activated by Generase I. (2008)
  • Author(s): Hayata D., et. al.
  • Journal Title: J. Biotechnol. 133 Pages: 478-85
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The functions and possible significance of Kremen as the gatekeeper of Wnt signaling in development and pathology. (2008)
  • Author(s): Nakamura T., et. al.
  • Journal Title: J. Cell. Mol. Med. 12 Pages: 391-408
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor improves synaptic localization of the NMDA receptor and intracellular signaling after excitotoxic injury in cultured hippocampal neurons. (2008)
  • Author(s): Akita H., et. al.
  • Journal Title: Exp. Neurol. 210 Pages: 83-94
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] NK4 gene therapy targeting HGF-Met and angiogenesis. (2008)
  • Author(s): Matsumoto K., et. al.
  • Journal Title: Front. Biosci. 13 Pages: 1943-1951
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Reduction of fibrosis in a rat model of non-alcoholic steatohepatitis cirrhosis by human HGF gene transfection using electroporation. (2008)
  • Author(s): Kiyama S., et. al.
  • Journal Title: J. Gastroenterol. Hepatol. (In press)(掲載確定)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hepatocyte Growth Factor and Met in Tumor Biology and Therapeutic Approach with NK4. (2008)
  • Author(s): Matsumoto K., et. al.
  • Journal Title: Proteomics (In press)(掲載確定)
  • NAID: 120001130499
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Generation of engineered recombinant hepatocyte growth factor cleaved and activated by Genenase I (2008)
  • Author(s): Hayata, D., Fukuta, K., Matsumoto, K., Adachi, E., Hanada, K., Adachi, K., Nakamura, T
  • Journal Title: J Biotechnol 133 Pages: 478-485
  • NAID: 120000811714
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hepatocyte growth factor improves synaptic localization of the NMDA receptor and intracellular signaling after excitotoxic injury in cultured hippocampal neurons (2008)
  • Author(s): Akita, H., Takagi, N., Ishihara, N., Takagi, K., Murotomi, K., Funakoshi, H., Matsumoto, K., Nakamura, T., Takeo, S
  • Journal Title: Exp Neurol 210(1) Pages: 83-94
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice (2008)
  • Author(s): Ito, W., Tanimoto, M., Ono, K., Mizuno, S., Yoshida, A., Koga, H., Fuchimoto, Y., Kondo, N., Tanimoto, Y., Kiura, K., Matsumoto, K., Kataoka, M., Nakamura, T., Gelfand, E., Kanehiro, A
  • Journal Title: Int. Arch. Allergy Immunol 145 Pages: 324-339
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Regulation of cell migration and cytokine production by HGF-like protein(HLP)/macrophage stimulating protein(MSP) in primary microglia (2008)
  • Author(s): Suzuki, Y., Funakoshi, H., Machide, M., Matsumoto, K., Nakamura, T
  • Journal Title: Biomed. Res 29 Pages: 77-84
  • NAID: 130004724052
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] NK4 gene therapy targeting HGF-Met and angiogenesis (2008)
  • Author(s): Matsumoto, K., Nakamura, T
  • Journal Title: Front Biosci 13 Pages: 1943-1951
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The functions and possible significance of Kremen as the gatekeeper of Wnt signaling in development and pathology (2008)
  • Author(s): Nakamura, T., Nakamura, T., Matsumoto, K
  • Journal Title: J. Cell. Mol. Med 12 Pages: 391-408
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hepatocyte growth factor as a renotrophic and anti-fibrotic regulator in chronic renal disease (2008)
  • Author(s): Mizuno, S., Matsumoto, K., Nakamura, T
  • Journal Title: Front. Biosci 13 Pages: 7072-7086
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Generation of engineered recombinant hepatocyte growth factor cleaved and activated by Generase I. (2008)
  • Author(s): Hayata D., et. al.
  • Journal Title: J.Biotechnol 133 Pages: 478-85
  • Peer Reviewed
• [Journal Article] The functions and possible significance of Kremen as the gatekeeper of Wnt signaling in development and pathology (2008)
  • Author(s): Nakamura T., et. al.
  • Journal Title: J.Cell.Mol.Med. (In press)
  • Peer Reviewed
• [Journal Article] Reduction of fibrosis in a rat model of non-alcoholic steatohepatitis cisshosis by human HGF gene transfection using electronoration (2008)
  • Author(s): Kiyama S., et. al.
  • Journal Title: J.Gastroenterol.Hepatol (In press)
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor improves synaptic localization of the NMDA receptor and intracellular signaling after excitotoxic injury incultured in cultured hippocarnpal neurons (2008)
  • Author(s): Akita H., et. al.
  • Journal Title: J.Neurochem (In press)
  • Peer Reviewed
• [Journal Article] NK4 gene therapy targeting HGF-Met and angiogenesis (2008)
  • Author(s): Matsumoto K., et. al.
  • Journal Title: Front.Biosci. (In press)
  • Peer Reviewed
• [Journal Article] Hepatocyte Growth Factor and Met in Tumor Biology and Therapeutic Approach with NK4 (2008)
  • Author(s): Matsumoto K., et. al.
  • Journal Title: Proteomics (In press)
  • NAID: 120001130499
  • Peer Reviewed
• [Journal Article] Inhibition of colon cancer growth and metastasis by NK4 gene repetitive delivery in mice. (2007)
  • Author(s): Wen J., et. al.
  • Journal Title: Biochem, Biophys. Res. Commun. 358 Pages: 117-123
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Stimulation of hepatocyte growth factor production by heparin-derived oligosaccharides. (2007)
  • Author(s): Sakiyama R., et. al.
  • Journal Title: J. Biochem. 141 Pages: 653-660
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A genomic analysis of adult T-cell leukemia. (2007)
  • Author(s): Choi Y. L., et. al.
  • Journal Title: Oncogene 26 Pages: 1245-1255
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor prevents pulmonary ischemia-reperfusion injury in mice. (2007)
  • Author(s): Makiuchi A., et. al.
  • Journal Title: J. Heart Lung Transplant. 26 Pages: 935-943
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells. (2007)
  • Author(s): Kanehira M., et. al.
  • Journal Title: Cancer Gene Ther. 14 Pages: 894-903
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice. (2007)
  • Author(s): Ito W., et. al.
  • Journal Title: Int. Arch. Allergy Immunol. 148 Pages: 324-339
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor promotes the number of PSD-95 clusters in young hippocampal neurons. (2007)
  • Author(s): Nakano M., et. al.
  • Journal Title: Exp. Neurol. 207 Pages: 195-202
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] NK4, an antagonist of hepatocyte growth factor(HGF), inhibits growth of multiple myeloma cells: Molecular targeting of angiogenic growth factor. (2007)
  • Author(s): Du W., et. al.
  • Journal Title: Blood 109 Pages: 3042-3049
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A genomic analysis of adult T-cell leukemia (2007)
  • Author(s): Choi, Y. L., Tsukasaki, K., O'neill, M., C., Yamada, Y., Onimaru, Y., Matsumoto, K., Ohashi, J., Yamashita, Y., Tsutsumi, S., Kaneda, R., Takada, S., Aburatani, H., Kamihira, S., Nakamura, T., Tomonaga, M., Mano, H
  • Journal Title: Oncogene 26 Pages: 1245-1255
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] NK4 gene therapy targeting HGF-Met and angiogenesis (2007)
  • Author(s): Matsumoto, K., Nakamura
  • Journal Title: In "Gene Therapy 2007" (eds, Ochiai, T., Shimada, H., Tagawa, M.) Pages: 22-33
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A genomic analysis of adult T-cell leukemia (2007)
  • Author(s): Choi, Y.L., Tsukasaki, K., O'neill, M.C., Yamada, Y., Onimaru, Y., Matsumoto, K., Ohashi, J., Yamashita, Y., Tsutsumi, S., Kaneda, R., Takada, S., Aburatani, H., Kamihira, S., Nakamura, T., Tomonaga, M., Mano, H
  • Journal Title: Oncogene 26 Pages: 1245-1255
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of colon cancer growth and metastasis by NK4 gene repetitive delivery in mice (2007)
  • Author(s): Wen, J., Matsumoto, K., Taniura, N., Tomioka, D., Nakamura, T
  • Journal Title: Biochem. Biophys. Res. Commun 358 Pages: 117-123
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Stimulation of Hepatocyte Growth Factor Production by Heparin-derived Oligosaccharides (2007)
  • Author(s): Sakiyama, R., Fukuta, K., Matsumoto, K., Furukawa, M., Takahashi, Y., Nakamura, T
  • Journal Title: J. Biochem 141 Pages: 653-660
  • NAID: 10020099195
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] NK4, an antagonist of hepatocyte growth factor (HGF), inhibits growth of multiple myeloma cells in vivo ; molecular targeting of angiogenic growth factor (2007)
  • Author(s): Du, W., Hattori, Y., Yamada, T., Matsumoto, K., Nakamura, T., Sagawa, M., Otsuki, T., Niikura, T., Nukiwa, T., Ikeda, Y
  • Journal Title: Blood 109 Pages: 3042-3049
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hepatocyte growth factor prevents pulmonary ischemia-reperfusion injury in mice (2007)
  • Author(s): Makiuchi, A., Yamaura, K., Mizuno, S., Matsumoto, K., Nakamura, T., Amano, J., Ito, K
  • Journal Title: J. Heart Lung Transplant Pages: 935-943
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells (2007)
  • Author(s): Kanehira, M., Xin, H., Hoshino, K., Maemondo, M., Mizuguchi, H., Hayakawa, T., Matsumoto, K., Nakamura, T., Nukiwa, T., Saijo, Y
  • Journal Title: Cancer Gene Ther 14 Pages: 894-903
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hepatocyte growth factor promotes the number of PSD-95 clusters in young hippocampal neurons (2007)
  • Author(s): Nakano, M., Takagi, N., Takagi, K., Funakoshi, H., Matsumoto, K., Nakamura, T., Takeo, S
  • Journal Title: Exp. Neurol 207(2) Pages: 195-202
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of colon cancer growth and metastasis by NK4 gene repetitive delivery in mice (2007)
  • Author(s): Wen J., et. al.
  • Journal Title: Biochem, Biophys.Res.Commun 358 Pages: 117-123
  • Peer Reviewed
• [Journal Article] Stimulation of hepatocyte growth factor production by heparin-derived oligosaccharides. (2007)
  • Author(s): Sakiyama R., et. al.
  • Journal Title: J.Biochem. 141 Pages: 653-660
  • Peer Reviewed
• [Journal Article] A genomic analysis of adult T-cell leukemia (2007)
  • Author(s): Choi Y. L., et. al.
  • Journal Title: Oncogene 26 Pages: 1245-1255
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor prevents pulmonary ischemia-reperfusion injury in mice (2007)
  • Author(s): Makiuchi A., et. al.
  • Journal Title: J. Heart Lung Transplant. 26 Pages: 935-943
  • Peer Reviewed
• [Journal Article] Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchvmal stem cells (2007)
  • Author(s): Kanehira M., et. al.
  • Journal Title: Cancer Gene Ther. 14 Pages: 894-903
  • Peer Reviewed
• [Journal Article] Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice (2007)
  • Author(s): Ito W., et. al.
  • Journal Title: Int.Arch.Allergy Immunol. 148 Pages: 324-339
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor promotes the number of PSD-95 clusters in young hippocampal neurons (2007)
  • Author(s): Nakano M., et. al.
  • Journal Title: Exp.Neurol. 207 Pages: 195-202
  • Peer Reviewed
• [Journal Article] NK4, an antagonist of hepatocyte growth factor(HGF),inhibits growth of multiple myeloma cells:Molecular targeting of angiogenic factor. (2007)
  • Author(s): Du W. et.al.
  • Journal Title: Blood 109 Pages: 3042-3049
  • Peer Reviewed
• [Journal Article] A genomic analysis of adult T-cell leukemia. (2007)
  • Author(s): Choi W.L.et al.
  • Journal Title: Oncogene 26 Pages: 1245-1255
• [Journal Article] Model of vasculogenesis from embryonic stem cells for vascular research and regenerative medicine. (2007)
  • Author(s): Nakagami H. et al.
  • Journal Title: Hypertension 48 Pages: 112-119
• [Journal Article] NK4, an antagonist of hepatocyte growth factor (HGF), inhibits growth of multiple myeloma cells in vivo; molecular targeting of angiogenic growth factor. (2007)
  • Author(s): Du W.et al.
  • Journal Title: Blood (In press)
• [Journal Article] Stimulation of Hepatocyte Growth Factor Production by Heparin-derived Oligosaccharides. (2007)
  • Author(s): Sakiyama. et al.
  • Journal Title: J. Hepatol. (In press)
• [Journal Article] Contact inhibition of hepatocyte growth factor regulated by functional association of the c-Met/HGF receptor and LAR protein tyrosine phosphatase. (2006)
  • Author(s): Machide M., et. al.
  • Journal Title: J. Biol. Chem. 281 Pages: 8765-8772
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Different acting regulation and sub-cellular localization of LIMK1 and LIMK2 during cell cycle transition. (2006)
  • Author(s): Sumi T., et. al.
  • Journal Title: Exp. Cell Res. 312 Pages: 1021-1030
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor and the Met system as a mediator in tumor-stromal interactions. (2006)
  • Author(s): Matsumoto K., et. al.
  • Journal Title: Int. J. Cancer 119 Pages: 477-483
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Preclinical study of a "tailor-made" combination of NK4-expressing gene therapy and gefitinib(ZD1839, Iressatrade mark)for disseminated peritoneal scirrhous gastric cancer. (2006)
  • Author(s): Namiki Y., et. al.
  • Journal Title: Int. J. Cancer 118 Pages: 1545-1555
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Enhanced suppression of tumor growth using a combination of NK4 plasmid DNA-PEG engrafted cationized dextran complex and ultrasound irradiation. (2006)
  • Author(s): Hosseinkhani H., et. al.
  • Journal Title: Cancer Gene Ther. 13 Pages: 479-489
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Angiogenetic and anti-fibrotic actions of hepatocyte growth factor improve cardiac dysfunction in porcine ischemic cardiomyopathy. (2006)
  • Author(s): Azuma J., et. al.
  • Journal Title: Gene Therapy 13 Pages: 1206-1213
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Peritumoral injection of adenovirus vector expressing NK4 combined withgemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival. (2006)
  • Author(s): Ogura Y., et. al.
  • Journal Title: Cancer Gene Ther. 13 Pages: 520-529
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Intraventricular administration of hepatocyte growth factor treats mouse communicating hydrocephalus induced by human recombinant TGF-betal. (2006)
  • Author(s): Tada T., et. al.
  • Journal Title: Neurobiol. Disease 21 Pages: 576-578
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Involvement of hepayocyte growth factor in the development of bone metastasis of a mouse mammary cancer cell line, BALB/c-MC. (2006)
  • Author(s): Ono K., et. al.
  • Journal Title: Bone 39 Pages: 27-34
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Prevention of apoptosis-inducing factor translocation is a possible mechanism for protective effects of hepatocyte growth factor against neuronal cell death in the hippocampus after transient forebrain ischemia. (2006)
  • Author(s): Niimura M., et. al.
  • Journal Title: J. Cereb. Blood Flow Met. 26 Pages: 1354-1365
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor attenuates cerebral ischemia-induced increase inpermeability of blood-brain barrier and decreases in expression of tight junctional proteins in cerebral vessels. (2006)
  • Author(s): Date I., et. al.
  • Journal Title: Neurosci Lett. 407 Pages: 141-145
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Liver targeting of plasmid DNA with a cationized pullulan for tumor suppression. (2006)
  • Author(s): JoJ., et. al.
  • Journal Title: J. Nano Sci. Nanotechnol. 6 Pages: 2853-2859
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Blockage of HGF/c-Met system by gene therapy(adenovirus-mediated NK4 gene)suppresses hepatocellular carcinoma in mice. (2006)
  • Author(s): Son G., et. al.
  • Journal Title: J. Hepatol. 45 Pages: 688-695
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity. (2006)
  • Author(s): Niimura M., et. al.
  • Journal Title: Neurosci Lett. 407 Pages: 136-140
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Contact inhibition of hepatocyte growth regulated by functional association of the c-Met/HGF receptor and LAR protein tyrosine phosphatase (2006)
  • Author(s): Machide, M., Hashigasako, A., Matsumoto, K., Nakamura, T
  • Journal Title: J. Biol. Chem 281 Pages: 8765-8772
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Preclinical study of a "tailor-made" combination of NK4-expressing gene therapy and gefitinib (ZD1839, Iressatrade mark) for disseminated peritoneal scirrhous gastric cancer (2006)
  • Author(s): Narniki, Y., Namiki, T., Yoshida, H., Date, M., Yashiro, M., Matsumoto, K., Nakamura, T., Yanagihara, K., Tada, N., Satoi, J., Fujise, K
  • Journal Title: Int. J. Cancer 118 Pages: 1545-1555
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Enhanced suppression of tumor growth using a combination of NK4 plasmid DNA-PEG engrafted cationized dextran complex and ultrasound irradiation (2006)
  • Author(s): Hosseinkhani, H., Kushibiki, T., Matsumoto, K., Nakamura, T., Tabata, Y
  • Journal Title: Cancer Gene Therapy 13 Pages: 479-489
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival (2006)
  • Author(s): Ogura, Y., Mizumoto, K., Nagai, E., Murakami, M., Inadome, N., Saimura, M., Matsumoto, K., Nakamura, T., Maemondo, M., Nukiwa, T., Tanaka, M
  • Journal Title: Cancer Gene Ther 13 Pages: 520-529
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of hepatocyte growth factor in the development of bone metastasis of a mouse mammary cancer cell line, BALB/c-MC (2006)
  • Author(s): Ono, K., Kamiya, S., Akatsu, T., Nakamura, C., Li, M., Amizuka, N., Matsumoto, K., Nakamura, T., Kugai, N., Wada, S
  • Journal Title: Bone 39 Pages: 27-34
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Different activity regulation and subcellular localization of LIMKI1 and LIMK2 during cell cycle transition (2006)
  • Author(s): Sumi, T., Hashigasako, A., Matsumoto, K., Nakamura, T
  • Journal Title: Exp. Cell Res 312 Pages: 1021-2030
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Intraventricular administration of hepatocyte growth factor treats mouse communicating hydrocephalus induced by transforming growth factor-β1 (2006)
  • Author(s): Tada, T., Zhan, H., Tanaka, Y., Hongo, K., Matsumoto, K., Nakamura, T
  • Journal Title: Neurobiol. Disease 21 Pages: 576-586
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Angiogenic and antifibrotic actions of hepatocyte growth factor improve cardiac dysfunction in porcine ischemic cardiomyopathy (2006)
  • Author(s): Azuma, J., Taniyama, Y., Takeya, Y., Iekushi, K., Aoki, M., Dosaka, N., Matsumoto, K., Nakamura, T., Ogihara, T., Morishita, R
  • Journal Title: Gene Therapy 13 Pages: 1206-1213
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Blockage of HGF/c-Met system by gene therapy (adenovirus-mediated NK4 gene) suppresses hepatocellular carcinoma in mice (2006)
  • Author(s): Son, G., Hirano, T., Seki, E., Iimuro, Y., Nukiwa, T., Matsumoto, K., Nakamura, T., Fujimoto, J
  • Journal Title: J. Hepatol 45 Pages: 688-695
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hepatocyte growth factor and the Met system as a mediator of tumor-stromal interactions (2006)
  • Author(s): Matsumoto, K., Nakamura, T
  • Journal Title: Int. J. Cancer 119 Pages: 477-483
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prevention of apoptosis-inducing factor translocation is a possible mechanism for protective effects of hepatocyte growth factor against neuronal cell death in the hippocampus after transient forebrain ischemia (2006)
  • Author(s): Niimura, M., Takagi, N., Takagi, K., Mizutani, R., Ishihara, N., Matsumoto, K., Funakoshi, H., Nakamura, T., Takeo, S
  • Journal Title: J. Cereb. Blood Flow Metab 26 Pages: 1354-1365
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Liver targeting of plasmid DNA with a cationized pullulan for tumor suppression (2006)
  • Author(s): Jo, J., Yamamoto, M., Matsumoto, K., Nakamura, T., Tabata, Y
  • Journal Title: J. Nanosci. Nanotechnol 6 Pages: 2853-2859
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity (2006)
  • Author(s): Niimura, M., Takagi, N., Takagi, K., Mizutani, R., Tanonaka, K., Funakoshi, H., Matsumoto, K., Nakamura, T., Takeo, S
  • Journal Title: Neurosci. Lett. 407 Pages: 136-140
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Model of vasculogenesis from embryonic stem cells for vascular research and regenerative medicine (2006)
  • Author(s): Nakagami, H., Nakagawa, N., Takeya, Y., Kashiwagi, K., Ishida, C., Hayashi, S., Aoki, M., Matsumoto, K., Nakamura, T., Ogihara, T., Morishita, R
  • Journal Title: Hypertension 48 Pages: 112-119
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hepatocyte growth factor attenuates cerebral ischemia-induced increase in permeability of the blood-brain barrier and decreases in expression of tight junctional proteins in cerebral vessels (2006)
  • Author(s): Date, I., Takagi, N., Takagi, K., Tanonaka, K., Funakoshi, H., Matsumoto, K., Nakamura, T., akeo, S
  • Journal Title: Neurosci. Lett. 407 Pages: 141-145
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contact inhibition of hepatocyte growth factor regulated by functional association of the c-Met/HGF receptor and LAR protein tyrosine phosphatase. (2006)
  • Author(s): Machide M. et al.
  • Journal Title: J. Biol. Chem. 281 Pages: 8765-8772
• [Journal Article] Different acting regulation and sub-cellular localization of LIMK1 and LIMK2 during cell cycle transition. (2006)
  • Author(s): Sumi T.et al.
  • Journal Title: Exp. Cell Res. 312 Pages: 1021-1030
• [Journal Article] Hepatocyte growth factor and the Met system as a mediator in tumor-stromal interactions (Review). (2006)
  • Author(s): Matsumoto K. et al.
  • Journal Title: Int. J. Cancer 119 Pages: 477-483
• [Journal Article] Preclinical study of a "tailor-made" combination of NK4-expressing gene therapy and gefitinib (ZD1839, Iressatrade mark) for disseminated peritoneal scirrhous gastric cancer. (2006)
  • Author(s): Namiki Y. et al.
  • Journal Title: Int. J. Cancer 118 Pages: 1545-1555
• [Journal Article] Enhanced suppression of tumor growth using a combination of NK4 plasmid DNA-PEG engrafted cationized dextran complex and ultrasound irradiation. (2006)
  • Author(s): Hosseinkhani H. et al.
  • Journal Title: Cancer Gene Ther. 13 Pages: 479-489
• [Journal Article] Angiogenetic and anti-fibrotic actions of hepatocyte growth factor improve cardiac dysfunction in porcine ischemic cardiomyopathy. (2006)
  • Author(s): Azuma J. et al.
  • Journal Title: Gene Therapy 13 Pages: 1206-1213
• [Journal Article] Peritumoral injection of adenovirus vector expressing NK4 combined with gemcitabine treatment suppresses growth and metastasis of human pancreatic cancer cells implanted orthotopically in nude mice and prolongs survival. (2006)
  • Author(s): Ogura Y. et al.
  • Journal Title: Cancer Gene Ther. 13 Pages: 520-529
• [Journal Article] Intraventricular administration of hepatocyte growth factor treats mouse communicating hydrocephalus induced by human recombinant TGF-betal. (2006)
  • Author(s): Tada T.et al.
  • Journal Title: Neurobiol. Disease 21 Pages: 576-578
• [Journal Article] Involvement of hepayocyte growth factor in the development of bone metastasis of a mouse mammary cancer cell line, BALB/c-MC. (2006)
  • Author(s): Ono K.et al.
  • Journal Title: Bone 39 Pages: 27-34
• [Journal Article] Prevention of apoptosis-inducing factor translocation is a possible mechanism for protective effects of hepatocyte growth factor against neuronal cell death in the hippocampus after transient forebrain ischemia. (2006)
  • Author(s): Niimura M. et al.
  • Journal Title: J. Cereb. Blood Flow Met. 26 Pages: 1354-1365
• [Journal Article] Hepatocyte growth factor attenuates cerebral ischemia-induced increase in permeability of blood-brain barrier and decreases in expression of tight junctional proteins in cerebral vessels. (2006)
  • Author(s): Date I.et al.
  • Journal Title: Neurosci Lett. 407 Pages: 141-145
• [Journal Article] Liver targeting of plasmid DNA with a cationized pullulan for tumor suppression. (2006)
  • Author(s): Jo J.et al.
  • Journal Title: J. Nano Sci. Nanotechnol. 6 Pages: 2853-2859
• [Journal Article] Blockage of HGF/c-Met system by gene therapy (adenovirus-mediated NK4 gene) suppresses hepatocellular carcinoma in mice. (2006)
  • Author(s): Son G.et al.
  • Journal Title: J. Hepatol. 45 Pages: 688-695
• [Journal Article] The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity. (2006)
  • Author(s): Niimura M. et al.
  • Journal Title: Neurosci Lett. 407 Pages: 136-140
• [Journal Article] Reduction of fibrosis in a rat model of non-alcoholic steatohepatitis cirrhosis by human HGF gene transfection using electroporation
  • Author(s): Kiyama, S., Yamada, T., Iwata, H., Sekino, T., Matsuo, H., Yoshida, N., Miyahara, T., Umeda, Y., Matsuno, Y., Kimura, M., Matsumoto, K., Nakamura, T., Takemura, H
  • Journal Title: J. Gastroenterol. Hepatol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hepatocyte Growth Factor and Met in Tumor Biology and Therapeutic Approach with NK4
  • Author(s): Matsumoto, K., Nakamura, T., Sakai, K., Nakamura, T
  • Journal Title: Proteomics (in press)
  • NAID: 120001130499
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] NK4による血管新生阻害機構:NK4による接着斑形成とフィブロネクチン構築の阻害 (2007)
  • Author(s): 酒井 克也
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] NK4による血管新生阻害機槽:NK4による接着斑形成とフィプロネクチン構築の阻害 (2007)
  • Author(s): 酒井 克也
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] JXM領域欠損型c-Met/HGFレセプターマウスでは、肝臓発生はおこったが、筋肉発育不全が認められた (2007)
  • Author(s): 中山 瑞穂
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] JXM領域欠損型c-MedHGFレセプターマウスでは、肝臓発生はおこったが、筋肉発育不全が認められた (2007)
  • Author(s): 中山 瑞穂
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] LARチロシンホスファターゼのプロセシングを介した細胞密度依存的な肝細胞増殖抑制機構 (2007)
  • Author(s): 町出 充
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] トリプトファン2,3-ジオキシゲナーゼ(TDO)ノックアウトは、情動行動と神経新生を修飾する (2007)
  • Author(s): 金井 将昭, ら
  • Organizer: 第80回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] LARチロシンポスファターゼのプロセシングを介した細胞密度依存的な肝細胞増殖抑制機構 (2007)
  • Author(s): 町出 充
  • Organizer: 第480回日本生化学会大会・第30回日本分子生物学会年会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] NK4による細胞外フィプロネクチン構築と接着斑形成の阻害. (2007)
  • Author(s): 酒井 克也
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] NK4は癌細胞-血管内皮細胞接着を阻害することでCT26肺転移を抑制する. (2007)
  • Author(s): 窪田 健
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] NK4による細胞外フィブロネクチン構築と接着斑形成の阻害 (2007)
  • Author(s): 酒井 克也
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] NK4は癌細胞一血管内皮細胞接蒲を阻害することでCT26肺転移を抑制する (2007)
  • Author(s): 窪田 健
  • Organizer: 第66回目本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] HGF-Met系を介した肝再生制御と疾患治療 (2007)
  • Author(s): 松本 邦夫
  • Organizer: 第4回日本病理学会カンファレンス
  • Place of Presentation: 旭川
  • Year and Date: 2007-07-27
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Inhibition of tumor metastasis and angiogenesis by NK4, bifunctional inhibitor of HGF-Met and angiogenesis (2007)
  • Author(s): Matsumoto K.
  • Organizer: 27th Sapporo Cancer Seminar International Symposium
  • Place of Presentation: Sapporo
  • Year and Date: 2007-07-12
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Inhibition of tumor metastasis and angiogenesis by NK4, bifunctional inhibitor of HGF-Met and angiogenesis (2007)
  • Author(s): Matsumoto K.
  • Organizer: 27th Sapporo Cancer Seminar Intermational Symposium
  • Place of Presentation: Sapporo
  • Year and Date: 2007-07-12
• [Presentation] 癌のNK4遺伝子治療の技術・意義と臨床試験に向けた開発状況 (2007)
  • Author(s): 松本 邦夫
  • Organizer: 第13回日本遺伝子治療学会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-30
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 癌のNK4遺伝子治療の鼓術・意義と臨床試験に向けた開発状況 (2007)
  • Author(s): 松本 邦夫
  • Organizer: 第13回日本遺伝テ治療学会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-30
• [Book] Electroporation Protocols(ed. S. Li)Springer (2008)
  • Author(s): Komamura K., et. al.
  • Total Pages: 11
  • Publisher: Hepatocyte growth factor gene therapy for hypertension.
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Electroporation Protocols(ed.S.Li)Springer (2008)
  • Author(s): Komamura K., et. al.
  • Total Pages: 11
  • Publisher: Hepatocyte growth factor gene therapy for hypertension
• [Book] Gene Therapy(edts T. Ochiai, H. Shimada and M. Tagawa), Cancer Japan Conference, Medical View Co. (2007)
  • Author(s): Matsumoto K., et. al.
  • Total Pages: 12
  • Publisher: NK4 gene therapy targeting HGF-Met and angiogenesis.
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 再生医療のための細胞生物学(関口清俊編) コロナ社 (2007)
  • Author(s): 松本 邦夫
  • Total Pages: 21
  • Publisher: 器官形成を制御する液性因子の生物学
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Gene Therapy(edts T.Ochiai, H.Shimada and M.Tagawa), Cancer JapanConference, Medical View Co. (2007)
  • Author(s): Matsumoto K., et. al.
  • Total Pages: 12
  • Publisher: NK4 gene therapy targeting HGF-Met and angiogenesis
• [Book] 再生医療のための細胞生物学(関口清俊編)コロナ社 (2007)
  • Author(s): 松本 邦夫
  • Total Pages: 21
  • Publisher: 器官形成を制御する擁性因子の生物学
• [Book] Gene Therapy 2007 (2007)
  • Author(s): Matsumoto K, Nakamura T
  • Total Pages: 12
  • Publisher: Medical View Co.
• [Book] 「細胞増殖因子と再生医療」 (2006)
  • Author(s): 松本邦夫
  • Total Pages: 15
  • Publisher: メディカルレビュー社(東京)
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 「細胞増殖因子と再生医療」 (2006)
  • Author(s): 松本邦夫、中村敏一
  • Total Pages: 8
  • Publisher: メディカルレビュー社(東京)
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 細胞増殖因子と再生医療 (2006)
  • Author(s): 松本邦夫
  • Total Pages: 15
  • Publisher: メディカルレビュー社(東京)
• [Book] 細胞増殖因子と再生医療 (2006)
  • Author(s): 松本邦夫, 中村敏一
  • Total Pages: 8
  • Publisher: メディカルレビュー社(東京)
• [Book] 再生医療のための細胞生物学 (2006)
  • Author(s): 松本邦夫
  • Total Pages: 22
  • Publisher: コロナ社
• [Patent(Industrial Property Rights)] 喘息治療剤 (2007)
  • Inventor(s): 金廣有彦、中村敏一、谷本光音、伊藤亘、 松本邦夫
  • Industrial Property Rights Holder: 中村敏一・クリングルファーマ
  • Acquisition Date: 2007-10-31
  • Overseas