1990 年度実績報告書

癌転移に関与する細胞側要因の解析

研究課題

研究課題/領域番号	02151041
研究機関	広島大学
研究代表者	横路謙次郎広島大学, 原爆放射能医学研究所, 教授 (70034618)
研究分担者	丹羽太貫広島大学, 原爆放射能医学研究所, 助教授 (80093293) 杉本芳一癌研究所化学療法センター, 研究員 (10179161) 村松喬鹿児島大学, 医学部, 教授 (00030891) 谷口俊一郎九州大学, 生体防御医学研究所, 助教授 (60117166) 竹市雅俊京都大学, 理学部, 教授 (00025454)
キーワード	癌転移 / 細胞接着分子 / 転移と糖蛋白質 / 癌遺伝子
研究概要	本班の目的は癌転移機構の解明に資する、主として分子レベルの基礎的デ-タを提供することにある。細胞表面蛋白について村松は、癌におけるレクチン結合糖鎖抗原を解析し、その特定のものとヒト癌患者での予後の相関を明らかにした。杉本は、血小板凝集能に相関する蛋白として44kdのものを同定し、これに対する抗体を用いてマウス実験系での転移の抑制が可能であることを示した。これら糖鎖抗原は腫瘍細胞が血管内で内皮細胞に接着し、微小転移巣を形成するのに重要である。竹市と永渕は、細胞接着因子カドヘリンとそれに相互作用する因子の関係を調べ、カテニンのリン酸化がカドヘリンの細胞接着作用に大きく影響すること、また細胞接着面でのカドヘリン結合蛋白を同定した。榎本はBalb/c3T3細胞で、vーsrcの導入により著明な転移性の上昇がみられる変異株を分離し、この変異は細胞の運動性を変えることを示した。谷口は、アクチンと転移について検討し、B16黒色腫ではβmアクチン、3Y1細胞ではαアクチンのそれぞれの発現低下が重要であることを示した。さらにvーfosの導入でみられる転移性の上昇に際してカテプシン、トロポミオシン、EF1αなどの細胞骨格関連蛋白の発現上昇をみており、これらの蛋白と転移性の関連という新しい研究の局面を切り開いた。仙波はerbB2遺伝子蛋白のN末からC末までの各々のドメインについて解析し、リン酸化酵素活性の制御機構の分子機構をほぼ明らかにした。現在erbB2のシグナルが核まで伝わるカスケ-ドを明らかにしつつある。横路と丹羽はマウス肉腫細胞株について遺伝子ラベル法で解析し、腫瘍細胞が内的に持っているgenetic instabilityと宿主の微小環境下でのselectionにより、腫瘍のclonal evolutionが起こることを明らかにした。三島は、ヒト悪性黒色腫に対する免疫療法について、積極的に研究を進めている。

研究成果
(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] <Niwa,O.>___ー,Kumazaki,T.,Tsukiyama,T.,Soma,G.,Miyajima N.& <Yokoro,K.>___ー: "A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line." Nucleic Acids Research. 18. 6709-6709 (1990)
[文献書誌] Enoki,Y.,<Niwa,O.>___ー,<Yokoro,K.>___ー& Toge,T.: "Analysis of clonal evolution in a tumor consist of pSV2neo transfected mouse fibrosarcoma clones." Japanese Journal of Cancer Research. 81. 141-147 (1990)
[文献書誌] Tsukiyama,T.,<Niwa,O.>___ー& <Yokoro,K.>___ー: "Characterization of the negative regulatory element of the 5′noncoding region of Moloney murine leukemia virus in mouse embryonal carcinoma cells." Virology. 177. 772-776 (1990)
[文献書誌] Yanagihara,K.,Seyama,T.,Tsumuraya,M.,Kamada,N.& <Yokoro,K.>___ー: "Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the cーmyc oncogene." Cancer Research. 51. 381-386 (1991)
[文献書誌] <Takeichi,M.>___ー: "Cadherins:A molecular family important in selective cellーcell adhesion." Annu.Rev.Biochem.59. 237-252 (1990)
[文献書誌] Nose,A.,Tsuji,K.& <Takeichi,M.>___ー: "Localization of specificity determining sites in cadherin adhesion molecules." Cell. 61. 147-155 (1990)
[文献書誌] <Takeichi,M.>___ー: "Cadherin cell adhesion receptors as a morphogentic regulator." Science.
[文献書誌] Furukawa,T.,Ozawa,M.,Huang,R.ーP.& <Muramatsu,T.>___ー: "A heparin binding protein whose expression increases during differentiation of embryonal carcinoma cells to parietal endoderm cells:cDNA cloning and sequence analysis." J.Biochem.108. 297-302 (1990)
[文献書誌] Kamada,Y.,Muramatsu,H.,Arita,Y.,Yamada,T.& <Muramatsu,T.>___ー: "Structural studies on a binding site for <Dolichos>___ー <Biflorus>___ー agglutinin in the small intestine of the mouse." J.Biochem.109. 178-183 (1991)
[文献書誌] <Sugimoto,Y.>___ー,Ohーhara,T.,Heike,Y.,Watanabe,M.,Nakatsuru,Y.,Ishikawa,T.& Tsuruo,T.: "Establishment of highly metastatic variants of murine colon adenocarcinoma 26 under serumーfree conditions." Int.J.Cancer. 46. 118-124 (1990)
[文献書誌] Yusa,K.,<Sugimoto,Y.>___ー,Yamori,T.,Yamamoto,T.,Toyoshima & Tsuruo,T.: "Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated cーerbBー2 gene." J.Natl.Cancer Inst.82. 1633-1636 (1990)
[文献書誌] <Sugimoto,Y.>___ー,Watanabe,M.,Ohーhara,T.,Sato,S.,Isoe,T.& Tsuruo,T.: "Suppression of experimental lung colonization of a metastatic variant of murine colon adenocarcinoma 26 by a monoclonal antibody 8Fll inhibiting tumor cellーinduced platelet aggregation." Cancer Research.
[文献書誌] <Taniguchi,S.>___ー,Nishimura,Y.,Takahashi,T.& Baba,T.: "Augmented excretion of procathepsin L of fosーtransferred highly metastatic rat cell line." Biochem.Biophys.Res.Comn.168. 520-526 (1990)
[文献書誌] Sadano,H.<Taniguchi,S.>___ー& Baba,T.: "Newly identified type of actin reduces invasiveness of mouse B16ーmelanoma." FEBS LETTERS. 271. 23-27 (1990)
[文献書誌] <Taniguchi,S.>___ー: "Biochemical analysis of newly identified actin in mouse B16ーmelanoma." Monograph of Pigment Cell Res.
[文献書誌] <Enomoto,T.>___ー,Ayaki,H.,Nakamori,S.,Enomoto,Y.,Inoue,H.& Kakunaga,T.: "Novel nonーtumorigenic cell variants showing potentially different susceptibility to vーsrcーinduced metastasis." Jpn.J.Cancer Res.81. 501-505 (1990)
[文献書誌] Hayashibe,K.,<Mishima,Y.>___ー& Ferrone,S.: "Molecular cloning and in vitro synthesis of a melanomaーassociated antigen immunogenic in patients." Proc.Natl.Acad.Sci.USA.
[文献書誌] <Semba,K.>___ー,Kawai,S.,Matsuzawa,Y.,Yamanashi,Y.,Nishizawa,M.& Toyoshima,K.: "Transformation of chiken embryo fibroblast cells by avian retroviruses containing the human fyn gene and its mutated genes." Mol.Cell.Biol.10. 3095-3104 (1990)

1990 年度実績報告書

癌転移に関与する細胞側要因の解析

研究代表者

横路謙次郎広島大学, 原爆放射能医学研究所, 教授 (70034618)

研究成果

[文献書誌] <Niwa,O.>_ー,Kumazaki,T.,Tsukiyama,T.,Soma,G.,Miyajima N.& <Yokoro,K.>_ー: "A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line." Nucleic Acids Research. 18. 6709-6709 (1990)

[文献書誌] Enoki,Y.,<Niwa,O.>_ー,<Yokoro,K.>_ー& Toge,T.: "Analysis of clonal evolution in a tumor consist of pSV2neo transfected mouse fibrosarcoma clones." Japanese Journal of Cancer Research. 81. 141-147 (1990)

[文献書誌] Tsukiyama,T.,<Niwa,O.>_ー& <Yokoro,K.>_ー: "Characterization of the negative regulatory element of the 5′noncoding region of Moloney murine leukemia virus in mouse embryonal carcinoma cells." Virology. 177. 772-776 (1990)

[文献書誌] Yanagihara,K.,Seyama,T.,Tsumuraya,M.,Kamada,N.& <Yokoro,K.>___ー: "Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the cーmyc oncogene." Cancer Research. 51. 381-386 (1991)

[文献書誌] <Takeichi,M.>___ー: "Cadherins:A molecular family important in selective cellーcell adhesion." Annu.Rev.Biochem.59. 237-252 (1990)

[文献書誌] Nose,A.,Tsuji,K.& <Takeichi,M.>___ー: "Localization of specificity determining sites in cadherin adhesion molecules." Cell. 61. 147-155 (1990)

[文献書誌] <Takeichi,M.>___ー: "Cadherin cell adhesion receptors as a morphogentic regulator." Science.

[文献書誌] Furukawa,T.,Ozawa,M.,Huang,R.ーP.& <Muramatsu,T.>___ー: "A heparin binding protein whose expression increases during differentiation of embryonal carcinoma cells to parietal endoderm cells:cDNA cloning and sequence analysis." J.Biochem.108. 297-302 (1990)

[文献書誌] Kamada,Y.,Muramatsu,H.,Arita,Y.,Yamada,T.& <Muramatsu,T.>_ー: "Structural studies on a binding site for <Dolichos>_ー <Biflorus>___ー agglutinin in the small intestine of the mouse." J.Biochem.109. 178-183 (1991)

[文献書誌] <Sugimoto,Y.>___ー,Ohーhara,T.,Heike,Y.,Watanabe,M.,Nakatsuru,Y.,Ishikawa,T.& Tsuruo,T.: "Establishment of highly metastatic variants of murine colon adenocarcinoma 26 under serumーfree conditions." Int.J.Cancer. 46. 118-124 (1990)

[文献書誌] Yusa,K.,<Sugimoto,Y.>___ー,Yamori,T.,Yamamoto,T.,Toyoshima & Tsuruo,T.: "Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated cーerbBー2 gene." J.Natl.Cancer Inst.82. 1633-1636 (1990)

[文献書誌] <Sugimoto,Y.>___ー,Watanabe,M.,Ohーhara,T.,Sato,S.,Isoe,T.& Tsuruo,T.: "Suppression of experimental lung colonization of a metastatic variant of murine colon adenocarcinoma 26 by a monoclonal antibody 8Fll inhibiting tumor cellーinduced platelet aggregation." Cancer Research.

[文献書誌] <Taniguchi,S.>___ー,Nishimura,Y.,Takahashi,T.& Baba,T.: "Augmented excretion of procathepsin L of fosーtransferred highly metastatic rat cell line." Biochem.Biophys.Res.Comn.168. 520-526 (1990)

[文献書誌] Sadano,H.<Taniguchi,S.>___ー& Baba,T.: "Newly identified type of actin reduces invasiveness of mouse B16ーmelanoma." FEBS LETTERS. 271. 23-27 (1990)

[文献書誌] <Taniguchi,S.>___ー: "Biochemical analysis of newly identified actin in mouse B16ーmelanoma." Monograph of Pigment Cell Res.

[文献書誌] <Enomoto,T.>___ー,Ayaki,H.,Nakamori,S.,Enomoto,Y.,Inoue,H.& Kakunaga,T.: "Novel nonーtumorigenic cell variants showing potentially different susceptibility to vーsrcーinduced metastasis." Jpn.J.Cancer Res.81. 501-505 (1990)

[文献書誌] Hayashibe,K.,<Mishima,Y.>___ー& Ferrone,S.: "Molecular cloning and in vitro synthesis of a melanomaーassociated antigen immunogenic in patients." Proc.Natl.Acad.Sci.USA.

[文献書誌] <Semba,K.>___ー,Kawai,S.,Matsuzawa,Y.,Yamanashi,Y.,Nishizawa,M.& Toyoshima,K.: "Transformation of chiken embryo fibroblast cells by avian retroviruses containing the human fyn gene and its mutated genes." Mol.Cell.Biol.10. 3095-3104 (1990)

1990 年度 実績報告書

癌転移に関与する細胞側要因の解析

研究代表者

横路 謙次郎 広島大学, 原爆放射能医学研究所, 教授 (70034618)

研究成果

[文献書誌] <Niwa,O.>___ー,Kumazaki,T.,Tsukiyama,T.,Soma,G.,Miyajima N.& <Yokoro,K.>___ー: "A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line." Nucleic Acids Research. 18. 6709-6709 (1990)

[文献書誌] Enoki,Y.,<Niwa,O.>___ー,<Yokoro,K.>___ー& Toge,T.: "Analysis of clonal evolution in a tumor consist of pSV2neo transfected mouse fibrosarcoma clones." Japanese Journal of Cancer Research. 81. 141-147 (1990)

[文献書誌] Tsukiyama,T.,<Niwa,O.>___ー& <Yokoro,K.>___ー: "Characterization of the negative regulatory element of the 5′noncoding region of Moloney murine leukemia virus in mouse embryonal carcinoma cells." Virology. 177. 772-776 (1990)

[文献書誌] Yanagihara,K.,Seyama,T.,Tsumuraya,M.,Kamada,N.& <Yokoro,K.>___ー: "Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the cーmyc oncogene." Cancer Research. 51. 381-386 (1991)

[文献書誌] <Takeichi,M.>___ー: "Cadherins:A molecular family important in selective cellーcell adhesion." Annu.Rev.Biochem.59. 237-252 (1990)

[文献書誌] Nose,A.,Tsuji,K.& <Takeichi,M.>___ー: "Localization of specificity determining sites in cadherin adhesion molecules." Cell. 61. 147-155 (1990)

[文献書誌] <Takeichi,M.>___ー: "Cadherin cell adhesion receptors as a morphogentic regulator." Science.

[文献書誌] Furukawa,T.,Ozawa,M.,Huang,R.ーP.& <Muramatsu,T.>___ー: "A heparin binding protein whose expression increases during differentiation of embryonal carcinoma cells to parietal endoderm cells:cDNA cloning and sequence analysis." J.Biochem.108. 297-302 (1990)

[文献書誌] Kamada,Y.,Muramatsu,H.,Arita,Y.,Yamada,T.& <Muramatsu,T.>___ー: "Structural studies on a binding site for <Dolichos>___ー <Biflorus>___ー agglutinin in the small intestine of the mouse." J.Biochem.109. 178-183 (1991)

[文献書誌] <Sugimoto,Y.>___ー,Ohーhara,T.,Heike,Y.,Watanabe,M.,Nakatsuru,Y.,Ishikawa,T.& Tsuruo,T.: "Establishment of highly metastatic variants of murine colon adenocarcinoma 26 under serumーfree conditions." Int.J.Cancer. 46. 118-124 (1990)

[文献書誌] Yusa,K.,<Sugimoto,Y.>___ー,Yamori,T.,Yamamoto,T.,Toyoshima & Tsuruo,T.: "Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated cーerbBー2 gene." J.Natl.Cancer Inst.82. 1633-1636 (1990)

[文献書誌] <Sugimoto,Y.>___ー,Watanabe,M.,Ohーhara,T.,Sato,S.,Isoe,T.& Tsuruo,T.: "Suppression of experimental lung colonization of a metastatic variant of murine colon adenocarcinoma 26 by a monoclonal antibody 8Fll inhibiting tumor cellーinduced platelet aggregation." Cancer Research.

[文献書誌] <Taniguchi,S.>___ー,Nishimura,Y.,Takahashi,T.& Baba,T.: "Augmented excretion of procathepsin L of fosーtransferred highly metastatic rat cell line." Biochem.Biophys.Res.Comn.168. 520-526 (1990)

[文献書誌] Sadano,H.<Taniguchi,S.>___ー& Baba,T.: "Newly identified type of actin reduces invasiveness of mouse B16ーmelanoma." FEBS LETTERS. 271. 23-27 (1990)

[文献書誌] <Taniguchi,S.>___ー: "Biochemical analysis of newly identified actin in mouse B16ーmelanoma." Monograph of Pigment Cell Res.

[文献書誌] <Enomoto,T.>___ー,Ayaki,H.,Nakamori,S.,Enomoto,Y.,Inoue,H.& Kakunaga,T.: "Novel nonーtumorigenic cell variants showing potentially different susceptibility to vーsrcーinduced metastasis." Jpn.J.Cancer Res.81. 501-505 (1990)

[文献書誌] Hayashibe,K.,<Mishima,Y.>___ー& Ferrone,S.: "Molecular cloning and in vitro synthesis of a melanomaーassociated antigen immunogenic in patients." Proc.Natl.Acad.Sci.USA.

[文献書誌] <Semba,K.>___ー,Kawai,S.,Matsuzawa,Y.,Yamanashi,Y.,Nishizawa,M.& Toyoshima,K.: "Transformation of chiken embryo fibroblast cells by avian retroviruses containing the human fyn gene and its mutated genes." Mol.Cell.Biol.10. 3095-3104 (1990)

1990 年度実績報告書

横路謙次郎広島大学, 原爆放射能医学研究所, 教授 (70034618)

[文献書誌] <Niwa,O.>_ー,Kumazaki,T.,Tsukiyama,T.,Soma,G.,Miyajima N.& <Yokoro,K.>_ー: "A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line." Nucleic Acids Research. 18. 6709-6709 (1990)

[文献書誌] Enoki,Y.,<Niwa,O.>_ー,<Yokoro,K.>_ー& Toge,T.: "Analysis of clonal evolution in a tumor consist of pSV2neo transfected mouse fibrosarcoma clones." Japanese Journal of Cancer Research. 81. 141-147 (1990)

[文献書誌] Tsukiyama,T.,<Niwa,O.>_ー& <Yokoro,K.>_ー: "Characterization of the negative regulatory element of the 5′noncoding region of Moloney murine leukemia virus in mouse embryonal carcinoma cells." Virology. 177. 772-776 (1990)

[文献書誌] Kamada,Y.,Muramatsu,H.,Arita,Y.,Yamada,T.& <Muramatsu,T.>_ー: "Structural studies on a binding site for <Dolichos>_ー <Biflorus>___ー agglutinin in the small intestine of the mouse." J.Biochem.109. 178-183 (1991)