Role of the matrix-degrading enzymes and their inhibitors on invasion and metastasis of oral SCC

基质降解酶及其抑制剂在口腔鳞状细胞癌侵袭和转移中的作用

• 批准号: 08672315
• 负责人: KAWAMATA Hitoshi
• 金额: $ 1.34万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672315/
• 关键词: oral SCC; invasion; metastasis; Cytokeratin 20; Tumor marker; matrix-degrading enzymes; TSC-22; Transfection; 転移; マイクロダイセリション; ザイモグラフィ; サイトケラチン; RT-PCR

We examined the expression of gelatinases and their inhibitors in human oral SCC cells, BHY (non-metastatic) and HN (metastatic). Both of the cells expressed several gelatinases. In addition, BHY cells secreted proMMP7 and procathepsin L,while HN cells secreted a large amount of active MMP2. HN cells secreted TIMP1, but only a trace level of TIMP2. The net activity of MMP2 and cathepsin L secreted from cancer cells may contribute respective to lymph node metastasis and the bone invasion of oral cancer cells.We examined the gelatinases in human oral SCC tissues by a microdissection-zymography. The gelatinolytic activities in cancer cell nests were much higher than those of normal gingival epithelium. The activities of active-MMP2 in cancer cell nests of metastatic cancers were significantly higher than those of non-metastatic cancers (p<0.05). We also examined the existence of circulating cancer cells in the peripheral blood of oral SCC patients by RT-PCR for cytokeratin 20 (CK20) mRNA.Eleven of 12 oral SCC patients showed positive results. However, there is no clear relationship of hematogenous CK20 mRNA for metastasis. All of the tumor-free survivors showed negative results. The expression of active-MMP2 in cancer cells can be used as a predictive marker for metastasis, and CK20 mRNA in peripheral blood can be used as a marker for tumor-recurrence in oral SCC patients.We isolated a growth suppressor gene, TSC-22. Then we analyzed the role of the gene on metastatic potentials of oral cancers. However, transfection of either sense or antisense TSC-22 gene did not affect the metastatic potentials of TYS cells. Futhermore, there was no significant difference in the expression of TSC-22 mRNA between metastatic oral cancers and none-metastatic oral cancers.

我们检测了明胶酶及其抑制剂在人口腔鳞癌细胞BHY（非转移性）和HN（转移性）中的表达。两种细胞都表达几种明胶酶。此外，BHY细胞分泌proMMP 7和前组织蛋白酶L，而HN细胞分泌大量活性MMP 2。HN细胞分泌TIMP 1，但仅分泌痕量水平的TIMP 2。癌细胞分泌的MMP 2和组织蛋白酶L的净活性可能分别与口腔癌细胞的淋巴结转移和骨侵袭有关。我们通过显微解剖-酶谱法检测了人类口腔SCC组织中的明胶酶。癌细胞巢中明胶酶活性明显高于正常牙龈上皮。转移癌细胞巢中MMP 2活性显著高于非转移癌细胞巢中MMP 2活性（p<0.05）。我们还通过RT-PCR检测了口腔SCC患者外周血中循环癌细胞的存在，检测细胞角蛋白20（CK 20）mRNA，12例口腔SCC患者中有11例呈阳性结果。然而，血行性CK 20 mRNA与转移之间没有明确的关系。所有无肿瘤存活者均显示阴性结果。在口腔鳞状细胞癌患者中，癌细胞中活性MMP 2的表达可作为肿瘤转移的预测指标，外周血中CK 20 mRNA的表达可作为肿瘤复发的预测指标。然后分析该基因在口腔癌转移潜能中的作用。然而，转染正义或反义TSC-22基因并不影响TYS细胞的转移潜能。此外，TSC-22 mRNA在转移性口腔癌和非转移性口腔癌中的表达无显著差异。

项目成果

Kawamata et al.: "Active MMP2 expression and hematogeneous cytokeratin 20 mRNA as a prodictive marker for metastasis and recurrence inoral cancer patients." British Journal of Cencer. (in press). (1998)

Kawamata 等人：“活性 MMP2 表达和血源性细胞角蛋白 20 mRNA 作为口腔癌患者转移和复发的预测标志物。”

Kawamata H,Uchida D,Hamano H,Kimura-Yanagawa T,Nakashiro K,Hino S,Omotehara F,Yoshida H and Sato M: "Active MMP2 expression and hematogeneous cytokeratin 20 mRNA as a predictive marker for metastasis and recurrence in oral cancer patients." British J Canc

Kawamata H、Uchida D、Hamano H、Kimura-Yanakawa T、Nakashiro K、Hino S、Omotehara F、Yoshida H 和 Sato M：“活性 MMP2 表达和血源性细胞角蛋白 20 mRNA 作为口腔癌患者转移和复发的预测标志物

Kawamata et al.: "Induction of TSC-22 by treatment with a new anti-cancer drug,vesnarinone,In a human salivary gland cancer" British Journal of Cancer. 77・1. 71-78 (1998)

Kawamata 等人：“用新的抗癌药物维纳里酮治疗人类唾液腺癌诱导 TSC-22”，《英国癌症杂志》77・1（1998 年）。

Kawamata et al.: "Active MMP2 expression and homatogeneous Cytokeratin 20 mRNA as a predictive marker for netastasis and recurrence in oral cancer pationt" British Journal of Cancer. (in press). (1998)

Kawamata 等人：“活性 MMP2 表达和同质细胞角蛋白 20 mRNA 作为口腔癌转移和复发的预测标记”《英国癌症杂志》。

Kawamata et al.: "Possible contribution of active MMP2 to lymph-nade metastasis and secreated cathepsin L to bone Invasion of heusly established oral squamous cancer cell lines." International Journal of Cancer. 70・1. 120-127 (1997)

Kawamata 等人：“活性 MMP2 对淋巴结转移和分泌的组织蛋白酶 L 对已建立的口腔鳞状癌细胞系的骨侵袭的可能贡献”，《国际癌症杂志》70·1 (1997)。