Participation of Stromal component in Cancer Progression

基质成分参与癌症进展

• 批准号: 12470439
• 负责人: HAYASHIDO Yasutaka
• 金额: $ 2.3万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470439/
• 关键词: oral cancer; invasion; metastasis; epithelial-mesenchymal interaction; fibroblast; cell motility; proteinase; matrix metalloproteinase; 繊維芽細胞; マトリックスメタロプテアーゼ; がん浸潤・転移; 細胞遊走

The invasion and metastasis of cancer cells has been proposed to be mediated by the surrounding microenvironment such as stromal cells and extracellular matrix proteins. We have demonstrated that fibroblasts secrete a chemotactic factor and enhance the motility of oral cancer cells. Tumor invasion and metastasis are also mediated by proteolytic enzymes that degrade extracellular matrix proteins. Matrix metalloproteinase-2 (MMP-2) degrades the major components of basement membrane such as type IV collagen, laminin and fibronectin. In various tumors including squamous cell carcinoma (SCC), increased production of MMP-2 has been associated their invasive and metastatic potential. However, MMPs including MMP-2, MMP-9 and stromelysin are not systematically secreted by tumor cells themselves but by nonmalignant stromal cells in the peritumoral host tissues.To assess the participation of stromal components in the proteolytic activity of SCC cells, we investigated the effect of fibroblasts on MMP-2 activation on the surface of SCC cells. SCC cells examined in this study serereted no MMP-2 and the plasma membrane of SCC cells failed to bind MMP-2 and activate it. However, treatment of SCC cells with fibroblast-conditioned medium (fibroblast-CM) led to the enhancement of MMP-2 binding and activation on the cell surface. Moreover, fibroblasts induced the expression of membrane type 1 MMP (MT1-MMP) in SCC cells. These findings suggest that fibroblasts might facilitate the invasion of SCC cells by increasing the proteolytic activity on the surfaces of SCC cells.

已经提出癌细胞的侵袭和转移由周围微环境如基质细胞和细胞外基质蛋白介导。我们已经证明，成纤维细胞分泌的趋化因子，并提高口腔癌细胞的运动。肿瘤侵袭和转移也由降解细胞外基质蛋白的蛋白水解酶介导。基质金属蛋白酶-2（MMP-2）降解基底膜的主要成分，如IV型胶原、层粘连蛋白和纤维连接蛋白。在包括鳞状细胞癌（SCC）在内的各种肿瘤中，MMP-2的产生增加与其侵袭和转移潜力相关。然而，MMP-2，MMP-9和基质溶解素等MMP并不是由肿瘤细胞本身系统地分泌，而是由癌旁宿主组织中的非恶性基质细胞分泌，为了评估基质成分参与SCC细胞的蛋白水解活性，我们研究了成纤维细胞对SCC细胞表面MMP-2活化的影响。本研究所检测的SCC细胞不分泌MMP-2，SCC细胞的质膜不能结合MMP-2并激活MMP-2，但用成纤维细胞条件培养液（fibroblast-CM）处理SCC细胞后，MMP-2在细胞表面的结合和激活增强。此外，成纤维细胞诱导SCC细胞膜型1 MMP（MT 1-MMP）的表达。这些结果表明，成纤维细胞可能通过增加SCC细胞表面的蛋白水解活性来促进SCC细胞的侵袭。

项目成果

Michimukai, E. et al.: "Mutations in the human homologue of the Drosophila segment polarity gene patched in oral squamous cell carcinoma cell lines"In Vitro Cell Dev. Biol. Anim.. 37(7). 459-464 (2001)

Michimukai，E.等人：“在口腔鳞状细胞癌细胞系中修补的果蝇节段极性基因的人类同源物中的突变”In Vitro Cell Dev。

Michimukai, E. et al.: "Mutations in the human homologue of the Drosophila segment polarity gene patched in oral squamous cell carcinoma cell lines"In Vitro Cell Dev. Biol. Anim.. 37(7). 464-459 (2001)

Michimukai，E.等人：“在口腔鳞状细胞癌细胞系中修补的果蝇节段极性基因的人类同源物中的突变”In Vitro Cell Dev。

Nii, M.et al.: "Suppression of Metastasis by Tissue Inhibitor of Metalloproteinase-1 in a Newly Established Human Oral Squamous Cell Carcinoma Cell Line"Int. J. Oncol.. 16. 119-124 (2000)

Nii，M.等人：“金属蛋白酶-1 组织抑制剂在新建立的人口腔鳞状细胞癌细胞系中抑制转移”Int。

Michimukai, E. et al.: "Mutations in the human homologue of the Drosophila segment polarity gene patched in oral squamous cell carcinoma cell lines"In Vitro Cell Dev.Biol.Anim.. 37(7). 459-464 (2001)

Michimukai，E.等人：“口腔鳞状细胞癌细胞系中修补的果蝇节段极性基因的人类同源物中的突变”In Vitro Cell Dev.Biol.Anim. 37(7)。

Yamanaka, T. et al.: "Isolation and Serum-free Culture of Epithelial Cells Derived from Epithelial Rests of Malassez in Human Periodontal Ligament"In Vitro Cell Dev. Biol. Anim.. 36(8). 548-553 (2000)

Yamanaka, T. 等人：“人牙周膜中马拉塞斯上皮残余物衍生的上皮细胞的分离和无血清培养”In Vitro Cell Dev。