Interaction of cancer cells with basement membrane proteins

2010 Fiscal Year Final Research Report

• Project/Area Number: 17014077
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Yokohama City University
• Principal Investigator: MIYAZAKI Kaoru Yokohama City University, 大学院・生命ナノシステム科学研究科, 教授 (70112068)
• Co-Investigator(Kenkyū-buntansha): HIGASHI Shouichi 横浜市立大学, 大学院・生命ナノシステム科学研究科, 准教授 (10275076)
• Co-Investigator(Renkei-kenkyūsha): OGAWA Takashi 横浜市立大学, 大学院・生命ナノシステム科学研究科, 特任助教 (80405018)
• Project Period (FY): 2005 – 2010
• Keywords: がん転移 / 基底膜 / 浸潤 / ラミニン / MMP

Research Abstract

Tumor microenvironments play important roles in tumor progression. The present study demonstrated that the cell adhesion protein laminin-332 (Lm332 ; α3β3γ2) in the basement membrane was converted to a soluble factor capable of strongly promoting tumor cell migration by a proteolytic cleavage of its γ2 chain (Lmγ2). We previously showed that Lmγ2 is solely overexpressed when carcinoma cells invade into stroma. Here, we found that the Lmγ2 expression was induced by TGF-β or some other factors and promoted invasive growth of tumor cells in vivo. Furthermore, we found a novel vascular laminin, laminin-3B11, that was down-regulated in tumor vasculature. The matrix metalloproteinase matrilysin (MMP7) is frequently overexpressed in many types of human cancer and involved in tumor progression and metastasis. Our results suggested that MMP7 might enhance tumor metastasis by binding to cholesterol sulfate of cell membrane and then cleaving cell surface proteins and Lm332. Lmγ2 and MMP7 seem to be good targets for anti-cancer treatments.

Research Products

• [Journal Article] Down-regulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers. (2011)
  • Author(s): Mori, T., Kariya, Y., Komiya, T., Higashi, S., Miyagi, Y., Sekiguchi, K., Miyazaki, K.
  • Journal Title: Cancer Sci. 102 Pages: 1095-1100
  • Peer Reviewed
• [Journal Article] Laminin-3B11, a novel vascular type laminin capable of inducing prominent lamellipodial protrusions in microvascular endothelial cells. (2010)
  • Author(s): Mori, T., Ono, K., Kariya, Y., Ogawa, T., Higashi, S., Miyazaki, K.
  • Journal Title: J.Biol.Chem. 285 Pages: 35068-35078
  • Peer Reviewed
• [Journal Article] Production of active MMP7 in E.Coli and its application for metalloproteinase inhibitors screening. (2010)
  • Author(s): Katsuno, H., Shirakawa, R., Miyazaki, K., Ozeki, Y., Yasumitsu, H.
  • Journal Title: Protein Peptide Lett. 17 Pages: 568-572
  • Peer Reviewed
• [Journal Article] Cholesterol sulfate alters substrate preference of matrix metalloproteinase-7 and promotes degradations of pericellular laminin-332 and fibronectin. (2010)
  • Author(s): Yamamoto, K., Miyazaki, K., Higashi, S.
  • Journal Title: J.Biol.Chem. 285 Pages: 28862-28873
  • Peer Reviewed
• [Journal Article] Expression of laminin gamma2 chain monomer enhances invasive growth of human carcinoma cells in vivo. (2010)
  • Author(s): Tsubota, Y., Ogawa, T., Oyanagi, J., Nagashima, Y., Miyazaki, K.
  • Journal Title: Int.J.Cancer 127 Pages: 2031-2041
  • Peer Reviewed
• [Journal Article] New marker proteins of the horny layer for evaluating the skin condition of patients with atopic dermatitis. (2009)
  • Author(s): Yamane, Y., Moriyama, K., Yasuda, C., Miyata, S., Aihara, M., Ikezawa, Z., Miyazaki, K.
  • Journal Title: Int.Arch.Allergy Immunol. 150 Pages: 89-101
  • Peer Reviewed
• [Journal Article] Matrilysin (MMP-7) cleaves C-type lectin domain family 3 member A (CLEC3A) on tumor cell surface and modulates its cell adhesion activity. (2009)
  • Author(s): Tsunezumi, J., Higashi, S., Miyazaki, K.
  • Journal Title: J.Cell.Biochem. 106 Pages: 693-702
  • Peer Reviewed
• [Journal Article] Idenitification of amino acid residues of matrix metalloproteinase-2 essential for its selective inhibition by beta-amyloid precursor protein-derived inhibitor. (2008)
  • Author(s): Higashi, S., Miyazaki, K.
  • Journal Title: J.Biol.Chem. 283 Pages: 10068-10078
  • Peer Reviewed
• [Journal Article] Localization of laminin alpha3B chain in vascular and epithelial basement membranes of normal human tissues and its down-regulation in skin cancers. (2008)
  • Author(s): Kariya Y, Mori T, Yasuda C, Watanabe N, Kaneko Y, Nakashima Y, Ogawa T, Miyazaki K.
  • Journal Title: J.Mol.Histol. 39 Pages: 435-446
  • Peer Reviewed
• [Journal Article] Matrilysin (matrix metallo- protease-7) cleaves membrane-bound annexin II and enhances binding of tissue-type plasminogen activator to cancer cell surfaces. (2008)
  • Author(s): Tsunezumi J, Yamamoto K, Higashi S, Miyazaki K.
  • Journal Title: FEBS J. 275 Pages: 4810-4823
  • Peer Reviewed
• [Journal Article] Identification of amino acid residues of matrix metalloproteinase-7 essential for binding to cholesterol sulfate. (2008)
  • Author(s): Higashi, S., Oeda, M., Yamamoto, K., Miyazaki, K.
  • Journal Title: J.Biol.Chem. 283 Pages: 35735-35744
  • Peer Reviewed
• [Journal Article] The β3 chain short arm of laminin-332 (laminin-5) induces matrix assembly and cell adhesion activity of laminin-511 (laminin-10). (2007)
  • Author(s): Nakashima, Y., Kariya, Y., Miyazaki, K.
  • Journal Title: J.Cell.Biochem. 100 Pages: 545-556
  • Peer Reviewed
• [Journal Article] The short arm of laminin.2 chain of laminin-5 (laminin-332) binds syndecan-1 and regulates cellular adhesion and migration by suppressing phosphorylation of integrin.4 chain. (2007)
  • Author(s): Ogawa, T., Tsubota, Y., Hashimoto, J., Miyazaki, K.
  • Journal Title: Mol.Biol.Cell 18 Pages: 1621-1633
  • Peer Reviewed
• [Journal Article] Strong suppression of tumor growth by insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1)/TAF/mac25. (2007)
  • Author(s): Sato, Y., Chen, Z., Miyazaki, K.
  • Journal Title: Cancer Sci. 98 Pages: 1055-1063
  • Peer Reviewed
• [Journal Article] Fatima Pedrosa Domellof, F.P. Laminins in keratoconus, bullous keratopathy, normal and scarred human corneas. Histochem. (2007)
  • Author(s): Bystrom, B., Virtanen, I., Rousselle, P., Miyazaki, K., Linden, C.
  • Journal Title: Cell Biol. 127 Pages: 657-667
  • Peer Reviewed
• [Journal Article] A novel function of syndecan-2, suppression of MMP-2 activation, which causes suppression of metastasis. (2007)
  • Author(s): Munesue S., Yoshitomi, Y., Kusano, Y., Koyama, Y., Nishiyama, A., Nakanishi, H., Miyazaki, K., Ishimaru, T., Miyaura, S., Okayama, M., Oguri, K.
  • Journal Title: J.Biol.Chem. 282 Pages: 28164-28174
  • Peer Reviewed
• [Journal Article] Acidic extracellular pH increases calcium influx-triggered phospholipase D activity along with acidic sphingomyelinase activation to induce matrix metalloproteinase-9 expression in mouse metastatic melanoma. (2007)
  • Author(s): Kato, Y., Ozawa, S., Tsukuda, M., Kubota, E., Miyazaki, K., St-Pierre, Y., Hata, R.
  • Journal Title: FEBS J. 274 Pages: 3171-3183
  • Peer Reviewed
• [Journal Article] Plasma membrane-associated sialidase (NEU3) differentially regulates integrin-mediated cell proliferation through laminin- and fibronectin-derived signaling. (2006)
  • Author(s): Kato, K., Shiga, K., Yamaguchi, K., Hata, K., Kobayashi, T., Miyazaki, K., Saijo, S., Miyagi, T.
  • Journal Title: Biochem.J. 394 Pages: 647-656
  • Peer Reviewed
• [Journal Article] Laminin-5 : Unique biological activity and role in tumor growth and invasion. (2006)
  • Author(s): Miyazaki, K.
  • Journal Title: Cancer Sci. 97 Pages: 91-98
  • Peer Reviewed
• [Journal Article] Reduced expression of laminin-5 in corneal epithelial cells under high glucose condition. (2006)
  • Author(s): Lu W, Ebihara N, Miyazaki K., Murakami A.
  • Journal Title: Cornea. 25 Pages: 61-67
  • Peer Reviewed
• [Journal Article] Identification of membrane-bound serine proteinase matriptase as processing enzyme of insulin-like growth factor binding protein-related rrotein-1 (2006)
  • Author(s): Ahmed, S., Jin, X., Yagi, M., Yasuda, C., Sato, Y., Higashi, S., Lin, C-Y., Dickson, R.B., Miyazaki, K.
  • Journal Title: IGFBP-rP1/angiomodulin/mac25.FEBS J. 273 Pages: 615-627
  • Peer Reviewed
• [Journal Article] Binding of active matrilysin to cell surface cholesterol sulfate is essential for its membrane-associated proteolytic action and induction of homotypic cell adhesion. (2006)
  • Author(s): Yamamoto , K., Higashi, S., Kioi, M., Tsunezumi, J., Honke, K., Miyazaki, K.
  • Journal Title: J.Biol.Chem. 281 Pages: 9170-9180
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor-1 induces migration and expression of laminin-5 in cultured human corneal epithelial cells. (2006)
  • Author(s): Lee, H. K., Lee, J. H., Kim, M., Kariya, Y., Miyazaki, K., Kim, E. K.
  • Journal Title: Invest.Ophthalmol.Vis.Sci. 47 Pages: 873-882
  • Peer Reviewed
• [Journal Article] Regulation of proliferation and chondrogenic differentiation of human mesenchymal stem cells by laminin-5 (laminin-332). (2006)
  • Author(s): Hashimoto, J., Kariya, Y., Miyazaki, K.
  • Journal Title: Stem Cells 24 Pages: 2346-2354
  • Peer Reviewed
• [Journal Article] Matriptase activates stromelysin (MMP-3) and promotes tumor growth and angiogenesis. (2006)
  • Author(s): Jin, X, J., Yagi, M., Akiyama, N., Hirosaki, T., Higashi, S., Lin, C-Y., Dickson, R.B., Kitamura, H., Miyazaki, K.
  • Journal Title: Cancer Sci. 97 Pages: 1327-1334
  • Peer Reviewed
• [Journal Article] N-acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyltransferase V on alpha 3beta 1 integrin-mediated cell migration.J. (2006)
  • Author(s): Zhao, Y., Nakagawa, T., Itoh, S., Inamori, K., Isaji T, Kariya, Y., Kondo, A., Miyoshi, E., Miyazaki, K., Kawasaki, N., Taniguchi, N., Gu, J.
  • Journal Title: Biol.Chem. 281 Pages: 32122-32130
  • Peer Reviewed
• [Journal Article] Deletion of core fucosylation on alpha3beta1 integrin down-regualtes its function. J. (2006)
  • Author(s): Zhao, Y., Itoh, S., Wang, X., Isaji, T., Miyoshi, E., Kariya Y, Miyazaki, K., Kawasaki, N., Taniguchi, N., Gu J.
  • Journal Title: Biol.Chem. 281 Pages: 38343-38350
  • Peer Reviewed
• [Journal Article] Production of soluble matriptase by human cancer cell lines and cell surface activation of its zymogen by trypsin. (2005)
  • Author(s): Jin, X., Hirosaki, T., Lin, C-Y, Dickson, R. B., Higashi, S., Kitamura, H., Miyazaki, K.
  • Journal Title: J.Cell.Biochem. 95 Pages: 632-647
  • Peer Reviewed
• [Journal Article] Regulation of biological activity and matrix assembly of laminin-5 by COOH-terminal, LG4-5 domain of alfa3 chain. (2005)
  • Author(s): Tsubota, Y., Yasuda, C., Kariya, Y., Ogawa, T., Hirosaki, T., Mizushima, H., Miyazaki, K.
  • Journal Title: J.Biol.Chem. 280 Pages: 14370-14377
  • Peer Reviewed
• [Journal Article] Regulation of matrix metalloproteinase-9 expression by extracellular pH in mouse metastatic melanoma cells. (2005)
  • Author(s): Kato, Y., Lambert, C. A., Colige, A. C., Mineur, P., Noel, A., Frankenne, F., Foidart, J-M., Baba, M., Hata, R., Miyazaki, K., Tsukuda, M.
  • Journal Title: J.Biol.Chem. 280 Pages: 10938-10944
  • Peer Reviewed
• [Journal Article] Ly6 family member C4.4A binds laminins 1 and 5, associates with galectin-3 and supports cell migration. (2005)
  • Author(s): Paret, C., Bourouba, M., Beer, A., Miyazaki, K., Schnolzer, M., Fiedler, S., Zoller, M.
  • Journal Title: Int.J.Cancer 115 Pages: 724-733
  • Peer Reviewed
• [Journal Article] Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes in an infant with Herlitz junctional epidermolysis bullosa (2005)
  • Author(s): Hata, D., Miyazaki, M., Seto, S., Kadota, E., Muso, E., Takasu, K., Nakano, A., Tamai, K., Uitto, J., Nagata, M., Moriyama, K., Miyazaki, K.
  • Journal Title: Pediatrics 116 Pages: 601-607
  • Peer Reviewed
• [Journal Article] Identification of proteins released by pancreatic cancer cells by multidimensional protein identification technology : a strategy for identification of novel cancer markers. (2005)
  • Author(s): Mauri, P., Scarpa, A., Nascimbeni, A. C., Benazzi, L., Parmagnani, E., Mafficini, A., Peruta, M. D., Bassi, C., Miyazaki, K., Sorio, C.
  • Journal Title: FASEB J. 19 Pages: 1125-1127
  • Peer Reviewed
• [Journal Article] Laminin-5 suppresses chondrogenic differentiation of murine teratocarcinoma cell line ATDC5. (2005)
  • Author(s): Hashimoto, J., Ogawa, T., Tsubota, Y., Miyazaki, K.
  • Journal Title: Exp.Cell.Res. 310 Pages: 256-269
  • Peer Reviewed
• [Journal Article] Regulation of cell adhesion and type VII collagen binding by beta3 chain short arm of laminin-5: effect of its proteolytic cleavage. (2005)
  • Author(s): Nakashima, Y., Kariya, Y., Yasuda, C., Miyazaki, K.
  • Journal Title: J.Biochem. 138 Pages: 539-552
  • Peer Reviewed
• [Journal Article] Uncoordinated production of Laminin-5 chains in airways epithelium of allergic asthmatics. Respir. (2005)
  • Author(s): Amin, K., Janson, C., Seveus, L., Miyazaki, K., Virtanen, I., Venge, P.
  • Journal Title: Res. 6 Pages: 110
  • Peer Reviewed
• [Journal Article] P.D.A simplified laminin nomenclature. (2005)
  • Author(s): Aumailley, M., Bruckner-Tuderman, L., Carter, W. G., Deutzmann, R., Edgar, D., Ekblom, P., Engel, J., Engvall, E., Hohenester, E., Jones, J. C., Kleinman, H. K., Marinkovich, M. P., Martin, G. R., Mayer, U., Meneguzzi, G., Miner, J. H., Miyazaki, K., Patarroyo, M., Paulsson, M., Quaranta, V., Sanes, J. R., Sasaki,T., Sekiguchi, K., Sorokin, L. M., Talts, J. F., Tryggvason, K., Uitto, J., Virtanen, I., von der Mark, K., Wewer, U. M., Yamada, Y., Yurchenco
  • Journal Title: Matrix Biol. 24 Pages: 326-332
  • Peer Reviewed
• [Journal Article] Differential expression of laminin isoforms in ovarian epithelial carcinomas suggesting different origin and providing tools for differential diagnosis. (2005)
  • Author(s): Maatta, M., Butzow, R., Luostarinen, J., Petajaniemi, N., Pihlajaniemi, T., Salo, S., Miyazaki, K., Autio-Harmainen, H., Virtanen I.
  • Journal Title: J.Histochem.Cytochem. 53 Pages: 1293-1300
  • Peer Reviewed
• [Remarks] ホームページ
  • URL: http://miyazaki.sci.yokohama-cu.ac.jp/
• [Patent(Industrial Property Rights)] ラミニン6B(ラミニン3B11)蛋白質 (2007)
  • Inventor(s): 宮崎香
  • Industrial Property Rights Holder: 公立大学法人横浜市立大学
  • Industrial Property Number: 特許,2007-028897
  • Filing Date: 2007-02-08
• [Patent(Industrial Property Rights)] ラミニン5を利用した間葉系幹細胞の培養技術 (2005)
  • Inventor(s): 宮崎香, 橋本絢子, 苅谷慶喜
  • Industrial Property Rights Holder: 公立大学法人横浜市立大学,財団法人木原記念横浜生命科学振興財団
  • Industrial Property Number: 特許,2005-240814
  • Filing Date: 2005-08-16