1991 年度実績報告書

がん細胞の浸潤性獲得の分子機構

研究課題

研究課題/領域番号	03151020
研究機関	金沢大学
研究代表者	清木元治金沢大学, がん研究所, 教授 (10154634)
研究分担者	木村成道東京都老人総合研究所, 主任研究員室長心得 (60073029) 谷口俊一郎九州大学, 生体防御医学研究所, 助教授 (60117166) 早川太郎愛知学院大学, 歯学部, 教授 (80064822) 宮崎香横浜市立大学, 木原生物学研究所, 助教授 (70112068) 岡田保典金沢大学, 医療技術短期大学部, 助教授 (00115221)
キーワード	浸潤転移 / がん悪性化 / メタロプロテア-ゼ / TIMP / NDPキナ-ゼ / βmアクチン
研究概要	清木班員は各種がん細胞株の産生するメタロプロテア-ゼのmRNA発現をノ-ザン法で調べ、また鶏卵胎児の肝臓へ転移したがん細胞での発現を免疫組織学的に調べることにより、がん細胞でのMMPー9の発現が鶏卵法での転移能と良く相関することを示した。佐藤班員はMMPー9遺伝子の発現制御領域を解析し、その発現が転写因子APー1,Spー1,NFーkBの結合部位を介して制御されることを示した。また、MMPー1、MMPー3遺伝子の制御領域との比較から、Spー1,NFーkBの結合部位を介するシグナルがMMPー9発現を誘導するために特徴的に必要とされることを明かにした。宮崎班員はインヒビタ-結合型MMPー2およびMMPー9がMMPー3によって効率良く活性化されることを示した。岡田班員はMMPー1、2、3、9とTIMPー1に対する単クロ-ン抗体を作成し、肺癌組織における発現を免疫組織学的に調べた。その結果、MMPー1とMMPー9が癌組織での主要酵素であり、TIMPー1との不均衡状態の存在を示した。早川班員はTIMPー2に特異的な単クロ-ン抗体を作成し、サンドイッチ酵素免疫測定法を確立した。谷口班員はβmアクチンが重合アクチンを安定化し、細胞運動能を低下させることにより転移能を抑制する可能性を示した。木村班員はヒトNDPキナ-ゼの2種のアイソフォ-ムに対応するラットホモロ-グcDNAを単離し、各組織での発現を調べた。ラットがん細胞の転移能との関係、シグナル伝達系への関与野解析を始めている。

研究成果

(19件)

すべてその他

すべて文献書誌 (19件)

[文献書誌] Y.ENDO: "Experimental metastasis of oncogene-transformed NIH3T3 cells in chick embryo" Jpn.J.Cancer Res.83. (1992)
[文献書誌] H.SATO: "Expression of genes encoding type IV collagendegrading metalloproteinases and tissue inhibitors of metalloproteinases in various human tumor cells" Oncogene. 7. 77-82 (1992)
[文献書誌] M.SEIKI: "Comparison of autocrine mechanisms promoting motility in two metastatic cell lines:human melanoma and rastransfected NIH3T3 cells" Int.J.Cancer. 49. 717-720 (1991)
[文献書誌] F.UMENISHI: "Efficient purification of TIMP-2 from culture medium conditioned by human hepatoma cell line,ans its inhibitory effects on metallo-proteinases and in vitro tumor invasion" J.Biochem.110. 189-195 (1991)
[文献書誌] K.ENJYOJI: "Characterization of rat factors X and Xa:demonstration of factor Xa in rat plasma" J.Biochem.109. 890-898 (1991)
[文献書誌] H.YASUMITU: "Comparison of extracellular matrix-degrading activities between 64-kDa and 90-kDa gelatinases purified in inhibitor-free forms from human schwannoma cells" J.Biochem.111. 74-80 (1992)
[文献書誌] Y.KATO: "Induction of 103-kDa gelatinase/type IV collagenase by acidic culture conditions in mouse metastatic melanoma cell lines" J.Biol.Chem.(1992)
[文献書誌] D.SAWAMURA: "Increased gene expression of matrix metalloproteinase 3 (stromelysin) in skin fibroblasts from patients with severe recessive dystrophic epidermolysis bullosa" Biochem.Biophys.Res.Commun.174. 1003-1008 (1991)
[文献書誌] Y.OKADA: "Localization of matrixmetalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium" Lab.Invest.(1992)
[文献書誌] J.KINISHI: "Purification and characterization of a new tissue inhibitor of metalloproteinases (TIMP-2) from mouse colon 26 tumor cells" Matrix. 11. 10-16 (1991)
[文献書誌] Y.FUKUDA: "Immunohistochemical study on tissue inhibitor of metalloproteinases in normal and pathological human livers" Gastroenterol.Jpn.26. 37-41 (1991)
[文献書誌] K.YAMASHITA: "Dissociation of collagenase-tissue inhibitor of metalloproteinases-1 (TIMP-1) complex-Its application for the independent measurements of TIMP-1 and collagenase activity in crude culture media and body fluids" Matrix. (1992)
[文献書誌] S.TANIGUCHI: "Biological and biochemical analysis of newly identified actin in mouse B16-melanoma" Pigment Cell Res.(1992)
[文献書誌] S.TANIGUCHI: "Rat elongation factor 1a:cDNA sequence and high expression in highly metastatic fos-transferred cell lines" Nucleic Acids Res.19. 6949-6954 (1992)
[文献書誌] J.SOMOLLE: "Relationship of tumor cell motility and morphologic patterns II.Analysis of tumor cell sublines with different motility in vitro" The American J.Dermat.(1992)
[文献書誌] H.SADANO: "Differential expression of vinculin between low and highly metastatic B16-melanoma cell lines" Jpn.J.Cancer Res.(1992)
[文献書誌] R.HIRAYAMA: "Positive relationship between expression of antimetastatic factor (nm23 gene product) and good prognosis in human breast cancer" J.Natl.Cancer Inst.83. 1249-1250 (1991)
[文献書誌] N.ISHIKAWA: "Isolation and characterization of a gene encoding rat nucleotide diphosphate kinase" J.Biol.Chem.(1991)
[文献書誌] K.ISHIDO: "Molecular cloning of cDNA for rat cathepsin C.Cathepsin C,a cysteine proteinase with an extremely long propeptide" J.Biol.Chem.266. 16312-16317 (1991)

1991 年度 実績報告書

がん細胞の浸潤性獲得の分子機構

研究代表者

清木 元治 金沢大学, がん研究所, 教授 (10154634)

研究成果

[文献書誌] Y.ENDO: "Experimental metastasis of oncogene-transformed NIH3T3 cells in chick embryo" Jpn.J.Cancer Res.83. (1992)

[文献書誌] H.SATO: "Expression of genes encoding type IV collagendegrading metalloproteinases and tissue inhibitors of metalloproteinases in various human tumor cells" Oncogene. 7. 77-82 (1992)

[文献書誌] M.SEIKI: "Comparison of autocrine mechanisms promoting motility in two metastatic cell lines:human melanoma and rastransfected NIH3T3 cells" Int.J.Cancer. 49. 717-720 (1991)

[文献書誌] F.UMENISHI: "Efficient purification of TIMP-2 from culture medium conditioned by human hepatoma cell line,ans its inhibitory effects on metallo-proteinases and in vitro tumor invasion" J.Biochem.110. 189-195 (1991)

[文献書誌] K.ENJYOJI: "Characterization of rat factors X and Xa:demonstration of factor Xa in rat plasma" J.Biochem.109. 890-898 (1991)

[文献書誌] H.YASUMITU: "Comparison of extracellular matrix-degrading activities between 64-kDa and 90-kDa gelatinases purified in inhibitor-free forms from human schwannoma cells" J.Biochem.111. 74-80 (1992)

[文献書誌] Y.KATO: "Induction of 103-kDa gelatinase/type IV collagenase by acidic culture conditions in mouse metastatic melanoma cell lines" J.Biol.Chem.(1992)

[文献書誌] D.SAWAMURA: "Increased gene expression of matrix metalloproteinase 3 (stromelysin) in skin fibroblasts from patients with severe recessive dystrophic epidermolysis bullosa" Biochem.Biophys.Res.Commun.174. 1003-1008 (1991)

[文献書誌] Y.OKADA: "Localization of matrixmetalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium" Lab.Invest.(1992)

[文献書誌] J.KINISHI: "Purification and characterization of a new tissue inhibitor of metalloproteinases (TIMP-2) from mouse colon 26 tumor cells" Matrix. 11. 10-16 (1991)

[文献書誌] Y.FUKUDA: "Immunohistochemical study on tissue inhibitor of metalloproteinases in normal and pathological human livers" Gastroenterol.Jpn.26. 37-41 (1991)

[文献書誌] K.YAMASHITA: "Dissociation of collagenase-tissue inhibitor of metalloproteinases-1 (TIMP-1) complex-Its application for the independent measurements of TIMP-1 and collagenase activity in crude culture media and body fluids" Matrix. (1992)

[文献書誌] S.TANIGUCHI: "Biological and biochemical analysis of newly identified actin in mouse B16-melanoma" Pigment Cell Res.(1992)

[文献書誌] S.TANIGUCHI: "Rat elongation factor 1a:cDNA sequence and high expression in highly metastatic fos-transferred cell lines" Nucleic Acids Res.19. 6949-6954 (1992)

[文献書誌] J.SOMOLLE: "Relationship of tumor cell motility and morphologic patterns II.Analysis of tumor cell sublines with different motility in vitro" The American J.Dermat.(1992)

[文献書誌] H.SADANO: "Differential expression of vinculin between low and highly metastatic B16-melanoma cell lines" Jpn.J.Cancer Res.(1992)

[文献書誌] R.HIRAYAMA: "Positive relationship between expression of antimetastatic factor (nm23 gene product) and good prognosis in human breast cancer" J.Natl.Cancer Inst.83. 1249-1250 (1991)

[文献書誌] N.ISHIKAWA: "Isolation and characterization of a gene encoding rat nucleotide diphosphate kinase" J.Biol.Chem.(1991)

[文献書誌] K.ISHIDO: "Molecular cloning of cDNA for rat cathepsin C.Cathepsin C,a cysteine proteinase with an extremely long propeptide" J.Biol.Chem.266. 16312-16317 (1991)

1991 年度実績報告書

清木元治金沢大学, がん研究所, 教授 (10154634)