1997 Fiscal Year Annual Research Report

宿主を重視した転移の分子生物学

Research Project

Project/Area Number	09254101
Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	The University of Tokyo
Principal Investigator	入村達郎東京大学, 大学院・薬学系研究科, 教授 (80092146)
Co-Investigator(Kenkyū-buntansha)	横田淳国立がんセンター研究所, 生物学部, 部長 (10191503) 谷口俊一郎信州大学, 医学部付属加齢適応研究所, 教授 (60117166) 矢守隆夫癌研究所癌化療センター, 基礎部, 副部長 (60200854) 松浦成昭大阪大学, 医学部, 教授 (70190402) 宮崎香横浜市立大学, 木原生物学研究所, 教授 (70112068)
Keywords	癌転移 / 血管新生 / 線維形成 / 自然免疫 / 微小環境 / 臓器特異性 / 細胞認識 / 液性因子
Research Abstract	癌の治療法を改善するには、癌がいかに宿主に障害を与えるかを明らかにする必要があり、転移の機構の解明もその重要な一環である。転移性を高める癌細胞の形質とその制御機構に基づく分子機構の解明が進んだ結果、転移の成立過程に於ける宿主因子の関与がより明確になってきた。転移形成の過程で、宿主由来の因子が、癌細胞の増殖性、運動性などを決定する表現形質に影響する。宿主細胞として関与する線維芽細胞など結合組織系の細胞、血管系の細胞、免疫系の細胞などは、液性因子によってお互いに交信しているだけでなく、直接の接着によって相互の関係を規定しあっている。本研究は、これらの宿主の組織と細胞に注目し、転移性癌細胞との相互作用を担う新しい転移決定分子の同定と、これに基づく新しい概念の提出を目的としている。宿主の血管系と癌細胞の相互作用に関して、血管新生におけるマトリックスプロテアーゼと低分子量接着分子の役割、血管内皮細胞や中皮細胞の細胞間開裂現象の背後にある細胞骨格系の制御機構特にリン酸化の重要性、脈管系構築に重要な分子であるカルポニンと転移との関連を明らかにした。組織の細胞外マトリクスや微小環境の転移における重要性に関して、肝転移の成立に関与する肝細胞由来細胞増殖因子とそのレセプター、癌の繊維化に関与する癌細胞由来の因子を同定した。また各種インデグリンが血行性転移形成とその臓器特異性を決定付けることを明らかにした。免疫系細胞の転移成立に置ける重要性に関して、マクロファージC型レクチンによる認識が卵巣癌のリンパ節転移に、T-細胞による認識がメラノーマ肺転移の形成に影響を持つことを示した。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Mizuochi,S.: "Uniqwe tissue distribution of a mouse macrophage C-type lectin." Glycobiology. 7. 137-146 (1997)
[Publications] Nakamori,S.: "Expression of carbohydrate ahtigen Sialyl Leaia new funtional Prognastic factor in gastic cancer." J.Clin.Oncol.15. 816-825 (1997)
[Publications] Yamamoto,K.: "Sialic acid-binding motif of Maackia amurensis lectins." J.Biochem. 121. 756-761 (1997)
[Publications] Nakamori,S.: "Inrolrement of carbohydrate antigen sialyl Lewis-x in colorectal cancer metastasis." Dis.Colon.Rectum.40. 420-431 (1997)
[Publications] Satoh,A.: "Modulation of cell surface lectin receptors on K562 human erythroleukemia cells induced by transfection with annexin IV cDNA" Febs.Let.405. 107-110 (1997)
[Publications] Koike,C.: "Tumor cells with organ-specific metastatic ability shows distinctive trafficking in riro:analyses by positron" Can.Res.57. 3612-3619 (1997)
[Publications] Nakamori,S.: "Increased endothelial cell retraction and tomor cell-inrasion by soluble factors derired from pancreatic cancer cells" Ann.Surg.Oncol.4. 361-368 (1997)
[Publications] Okamoto,H.: "Down-regulation of focal adnesion kinase pp125FAK in endothelial cells retraction durirg Tumor cell inrasion" Clin.Exp.Metastasis. in press (1998)
[Publications] Tumura,S.: "Association of ccmulative allelic losses with tumor aggressireness in hepatocellular Carcinoma." J.Hepatol. 27. 669-676 (1997)
[Publications] Aihara,T.: "Derection of pancreatic and gastric cancer cells in peripheral ard postal blood by amplitication of Keratin 19 mRNA" Int.I.Cancer. 72. 408-411 (1997)
[Publications] Hashimoto,Y: "Expression of the Elml gene,a novel gene of CCN family Soppresses in rivo-tomor growth and metastasta sps of K1735" J.Exp.Med.in press (1998)
[Publications] Tari,M.: "Isolation of novel Sry-related gene that is expressed in high-melastatic k-1735 murine melanoma cells." Genomics. 39. 30-37 (1997)
[Publications] Yamashita,T.: "Reciprocal control of colon-specific sulfomucin and sialosyl Tn antigen expression in human colorectal neoplasia" Virchows.Arch,. 431. 25-30 (1997)
[Publications] Kimura,H.: "Distinct substrate specificities of five human α-1,3-fucosyltransferases for in viro synthesis of the sialyl Lenres" Biol.Biophy,Res.Com.237. 131-137 (1997)
[Publications] Fukuda,S.: "Isolation of a norel gone showing reduced expression in metastatic colorectal carinoma cell and corcinoma" Jpn.J.Cancer Res.88. 725-731 (1997)
[Publications] Lim.J: "Isolation of murine and human homolog use of the fission-yeast dis3t gene encoding a mitotic-control protein" Cancer.Res.57. 921-925 (1997)
[Publications] Yamori,T.: "Anti-tumor efficacy of poclitaxel against human lung cancer xenografts" Jpn.J.Cancer Res.88. 1205-1210 (1997)
[Publications] Fujii,H.: "Vaccination with B7-1+Tumor and anti-adhesion therapy with RGD pseudo-pepride(Fc-336)efficiently induce anti-metastatic effect." Clinical.Exp.Metastasis. 16(in press). (1998)

1997 Fiscal Year Annual Research Report

宿主を重視した転移の分子生物学

Principal Investigator

入村 達郎 東京大学, 大学院・薬学系研究科, 教授 (80092146)

Research Products

[Publications] Mizuochi,S.: "Uniqwe tissue distribution of a mouse macrophage C-type lectin." Glycobiology. 7. 137-146 (1997)

[Publications] Nakamori,S.: "Expression of carbohydrate ahtigen Sialyl Leaia new funtional Prognastic factor in gastic cancer." J.Clin.Oncol.15. 816-825 (1997)

[Publications] Yamamoto,K.: "Sialic acid-binding motif of Maackia amurensis lectins." J.Biochem. 121. 756-761 (1997)

[Publications] Nakamori,S.: "Inrolrement of carbohydrate antigen sialyl Lewis-x in colorectal cancer metastasis." Dis.Colon.Rectum.40. 420-431 (1997)

[Publications] Satoh,A.: "Modulation of cell surface lectin receptors on K562 human erythroleukemia cells induced by transfection with annexin IV cDNA" Febs.Let.405. 107-110 (1997)

[Publications] Koike,C.: "Tumor cells with organ-specific metastatic ability shows distinctive trafficking in riro:analyses by positron" Can.Res.57. 3612-3619 (1997)

[Publications] Nakamori,S.: "Increased endothelial cell retraction and tomor cell-inrasion by soluble factors derired from pancreatic cancer cells" Ann.Surg.Oncol.4. 361-368 (1997)

[Publications] Okamoto,H.: "Down-regulation of focal adnesion kinase pp125FAK in endothelial cells retraction durirg Tumor cell inrasion" Clin.Exp.Metastasis. in press (1998)

[Publications] Tumura,S.: "Association of ccmulative allelic losses with tumor aggressireness in hepatocellular Carcinoma." J.Hepatol. 27. 669-676 (1997)

[Publications] Aihara,T.: "Derection of pancreatic and gastric cancer cells in peripheral ard postal blood by amplitication of Keratin 19 mRNA" Int.I.Cancer. 72. 408-411 (1997)

[Publications] Hashimoto,Y: "Expression of the Elml gene,a novel gene of CCN family Soppresses in rivo-tomor growth and metastasta sps of K1735" J.Exp.Med.in press (1998)

[Publications] Tari,M.: "Isolation of novel Sry-related gene that is expressed in high-melastatic k-1735 murine melanoma cells." Genomics. 39. 30-37 (1997)

[Publications] Yamashita,T.: "Reciprocal control of colon-specific sulfomucin and sialosyl Tn antigen expression in human colorectal neoplasia" Virchows.Arch,. 431. 25-30 (1997)

[Publications] Kimura,H.: "Distinct substrate specificities of five human α-1,3-fucosyltransferases for in viro synthesis of the sialyl Lenres" Biol.Biophy,Res.Com.237. 131-137 (1997)

[Publications] Fukuda,S.: "Isolation of a norel gone showing reduced expression in metastatic colorectal carinoma cell and corcinoma" Jpn.J.Cancer Res.88. 725-731 (1997)

[Publications] Lim.J: "Isolation of murine and human homolog use of the fission-yeast dis3t gene encoding a mitotic-control protein" Cancer.Res.57. 921-925 (1997)

[Publications] Yamori,T.: "Anti-tumor efficacy of poclitaxel against human lung cancer xenografts" Jpn.J.Cancer Res.88. 1205-1210 (1997)

[Publications] Fujii,H.: "Vaccination with B7-1+Tumor and anti-adhesion therapy with RGD pseudo-pepride(Fc-336)efficiently induce anti-metastatic effect." Clinical.Exp.Metastasis. 16(in press). (1998)

入村達郎東京大学, 大学院・薬学系研究科, 教授 (80092146)