2003 Fiscal Year Annual Research Report

フラクタルカインおよびレセプター発現と癌の悪性度・転移との関連

Research Project

Project/Area Number	15024236
Research Institution	Kyoto University
Principal Investigator	梅原久範京都大学, 医学研究科, 助教授 (70247881)
Co-Investigator(Kenkyū-buntansha)	今井俊夫カン研究所, 所長岡崎俊朗京都大学, 医学研究科, 講師 (40233308)
Keywords	フラクタルカイン / 転移 / 細胞接着 / 浸潤 / IFN-γ / 細胞傷害 / 悪性度
Research Abstract	癌の悪住度は,転移の頻度および抗癌剤や腫瘍殺傷能を有する免疫担当細胞に対する感受性などにより規定される.フラクタルカインは細胞接着と遊走活性を合わせ持つケモカインで細胞の接着と遊走に深く関わっている.腫瘍細胞におけるフラクタルカイン発現は細胞傷害性T細胞に対する感受性を示し,癌の遊走と転移および免疫担当細胞に対する抵抗性など癌の悪性度に深く関わっている.我々は,1)フラクタルカインレセプター(CX3CR1)がNK細胞とCD8陽性T細胞に発現していること,2)フラクタルカインが接着分子と協調的に細胞接着を誘導すること,3)フラクタルカインが選択的にCD8陽性T細胞やNK細胞を遊走させること,5)フラクタルカインがNK細胞から傷害顆粒を放出させること,6)フラクタルカイン発現癌細胞がNK細胞に高い感受性を示すこと,7)固層化フラクタルカインがNK細胞を活性化しIFN-γ産生を増強することを明らかにした.このように,腫瘍細胞がフラクタルカインを発現している場合には,CD8陽性T細胞やNK細胞により傷害を受け除去され,逆にCX3CR1を発現している場合には,内皮細胞との接着増強,フラクタルカインによる遊走増強を受け,浸潤や転移が増強する可能性がある.

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Yamaoka S, et al.: "Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells"J Biol Chem. (印刷中).
[Publications] Uchida Y, et al.: "Anthracycline resistance in HL-60/ADR cells via transcriptional up-regulatio of glucosylceramide synthase and reversal by Sp1 decoyoligodeoxynucleotides"J.Biol.Chem. (印刷中).
[Publications] Umehara H, et al.: "Fractalkine and vascular biology : from basic research to clinical diseases."Arterio.Thromb.Vasc.Biol.(Review).. 24. 34-40 (2004)
[Publications] Watanabe I, et al.: "Increase of ceramide content in nuclei through caspase-3 dependent inhibition of sphingomyelin synthase in Fas-induced Jurkat T cell apoptosis"Cancer Res.. 60. 1000-1007 (2004)
[Publications] Kawabata D, et al.: "Ameliorative effects of follistatin-related protein/TSC-36 on joint inflammation in a mouse model of arthritis."Arthritis Rheum. 50. 660-607 (2004)
[Publications] Iwai K, et al.: "Ceramide increases oxidative damage due to inhibition of catalase by caspase-3-dependent proteolysis in HL-60 cell apoptosis."J.Biol.Chem.. 278. 9813-9822 (2003)
[Publications] Yoneda O, et al.: "Membrane bound form of fractalkine induces IFN-γ production by NK cells : A role for Th1 response."Eur.J.Immunol.. 33. 53-58 (2003)
[Publications] Umehara H, et al.: "Role for adapter proteins in costimulatory signals of CD2 and IL-2 on NK cell activation."Mol.Immunol.. 38. 587-596 (2002)
[Publications] Tanaka Y, et al.: "H-Ras/Mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts."J.Biol.Chem.. 277. 21446-21452 (2002)
[Publications] Nishimura M, et al.: "Dualfunctions of fractalkine/CX3CR1 in trafficking of circulating cytotoxic effector lymphocytes that are defined by CX3CR1 expression."J.Immunol.. 168. 6173-6180 (2002)
[Publications] Kondo T, et al.: "Vesnarinone causes oxidative damage by inhibiting catalase function through ceramide action in myeloid cell apoptosis."Mol.Pharm.. 61. 620-627 (2002)
[Publications] Kondo T, et al.: "Control of ceramide-induced apoptosis by IGF-1 : involvement of PI-3 kinase caspase-3 and catalase."Cell Death Differnt. 9. 682-692 (2002)
[Publications] Kawase M, et al.: "Increase of ceramide in adriamycin-induced HL-60 cell apoptosis : detection by a novel anti-ceramide antibody."Biochemica et Biophysica Acta. 1584. 104-114 (2002)
[Publications] Inoue H, et al.: "Lipid rafts as the signaling scaffold for NK cell activation : Tyrosine phosphorylation and association of LAT with phosphatidylinositol 3-kinase and PLC-γ following CD2 stimulation."Eur.J.Immunol.. 32. 2188-2198 (2002)

2003 Fiscal Year Annual Research Report

フラクタルカインおよびレセプター発現と癌の悪性度・転移との関連

Principal Investigator

梅原 久範 京都大学, 医学研究科, 助教授 (70247881)

Research Products

[Publications] Yamaoka S, et al.: "Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells"J Biol Chem. (印刷中).

[Publications] Uchida Y, et al.: "Anthracycline resistance in HL-60/ADR cells via transcriptional up-regulatio of glucosylceramide synthase and reversal by Sp1 decoyoligodeoxynucleotides"J.Biol.Chem. (印刷中).

[Publications] Umehara H, et al.: "Fractalkine and vascular biology : from basic research to clinical diseases."Arterio.Thromb.Vasc.Biol.(Review).. 24. 34-40 (2004)

[Publications] Watanabe I, et al.: "Increase of ceramide content in nuclei through caspase-3 dependent inhibition of sphingomyelin synthase in Fas-induced Jurkat T cell apoptosis"Cancer Res.. 60. 1000-1007 (2004)

[Publications] Kawabata D, et al.: "Ameliorative effects of follistatin-related protein/TSC-36 on joint inflammation in a mouse model of arthritis."Arthritis Rheum. 50. 660-607 (2004)

[Publications] Iwai K, et al.: "Ceramide increases oxidative damage due to inhibition of catalase by caspase-3-dependent proteolysis in HL-60 cell apoptosis."J.Biol.Chem.. 278. 9813-9822 (2003)

[Publications] Yoneda O, et al.: "Membrane bound form of fractalkine induces IFN-γ production by NK cells : A role for Th1 response."Eur.J.Immunol.. 33. 53-58 (2003)

[Publications] Umehara H, et al.: "Role for adapter proteins in costimulatory signals of CD2 and IL-2 on NK cell activation."Mol.Immunol.. 38. 587-596 (2002)

[Publications] Tanaka Y, et al.: "H-Ras/Mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts."J.Biol.Chem.. 277. 21446-21452 (2002)

[Publications] Nishimura M, et al.: "Dualfunctions of fractalkine/CX3CR1 in trafficking of circulating cytotoxic effector lymphocytes that are defined by CX3CR1 expression."J.Immunol.. 168. 6173-6180 (2002)

[Publications] Kondo T, et al.: "Vesnarinone causes oxidative damage by inhibiting catalase function through ceramide action in myeloid cell apoptosis."Mol.Pharm.. 61. 620-627 (2002)

[Publications] Kondo T, et al.: "Control of ceramide-induced apoptosis by IGF-1 : involvement of PI-3 kinase caspase-3 and catalase."Cell Death Differnt. 9. 682-692 (2002)

[Publications] Kawase M, et al.: "Increase of ceramide in adriamycin-induced HL-60 cell apoptosis : detection by a novel anti-ceramide antibody."Biochemica et Biophysica Acta. 1584. 104-114 (2002)

[Publications] Inoue H, et al.: "Lipid rafts as the signaling scaffold for NK cell activation : Tyrosine phosphorylation and association of LAT with phosphatidylinositol 3-kinase and PLC-γ following CD2 stimulation."Eur.J.Immunol.. 32. 2188-2198 (2002)

梅原久範京都大学, 医学研究科, 助教授 (70247881)