Matrisian L M, Wright J, Newell K, Witty J P
Department of Cell Biology, Vanderbilt University, Nashville, TN 37232, USA.
Princess Takamatsu Symp. 1994;24:152-61.
The matrix-degrading metalloproteinases (MMPs) have been implicated in tumor invasion and metastasis. Recently it has become clear that the expression of MMPs in tumors is frequently localized to stromal cells surrounding malignant tumor cells. In the mouse skin model of multi-stage carcinogenesis, the MMP stromelysin is expressed in stromal fibroblast-like cells surrounding benign and malignant squamous cell carcinomas. Conversion of these tumors to highly invasive and metastatic spindle-cell tumors is however, associated with the expression of stromelysin-1 mRNA in the tumor cells themselves. The analysis of MMPs in human colon adenocarcinomas at different stages of tumor progression revealed that matrilysin was the only MMP expressed in the tumor cells, while stromelysin-1 and stromelysin-3 mRNA was detected in stromal cells surrounding malignant tumor cells. Matrilysin mRNA is detected in benign tumors as well as malignant tumor cells, and the relative level and percent of tumors expressing matrilysin correlates with the stage of tumor progression. These results suggest that both stromal and tumor cell metalloproteinases may contribute to tumor invasion and metastasis, and also suggests that MMPs may play a role in earlier events in the tumor progression pathway. A potential role for MMPs in tumor growth is illustrated by results which suggest that the expression of matrilysin in human colon cancer-derived cells increases tumorigenicity following injection into the cecum, and that transgenic mice expressing matrilysin mRNA show a marked proliferative response. MMPs may therefore play multiple roles in tumor progression.
基质降解金属蛋白酶（MMPs）与肿瘤侵袭和转移有关。最近已明确，MMPs在肿瘤中的表达通常定位于恶性肿瘤细胞周围的基质细胞。在多阶段致癌作用的小鼠皮肤模型中，MMP基质溶解素在良性和恶性鳞状细胞癌周围的基质成纤维细胞样细胞中表达。然而，这些肿瘤转变为高侵袭性和转移性的梭形细胞肿瘤与肿瘤细胞自身中基质溶解素-1 mRNA的表达有关。对处于肿瘤进展不同阶段的人类结肠腺癌中MMPs的分析显示，基质溶素是肿瘤细胞中唯一表达的MMP，而在恶性肿瘤细胞周围的基质细胞中检测到基质溶解素-1和基质溶解素-3 mRNA。在良性肿瘤以及恶性肿瘤细胞中均检测到基质溶素mRNA，并且表达基质溶素的肿瘤的相对水平和百分比与肿瘤进展阶段相关。这些结果表明，基质和肿瘤细胞金属蛋白酶都可能促进肿瘤侵袭和转移，也表明MMPs可能在肿瘤进展途径的早期事件中发挥作用。MMPs在肿瘤生长中的潜在作用体现在以下结果中：在人结肠癌衍生细胞中基质溶素的表达在注入盲肠后增加了致瘤性，并且表达基质溶素mRNA的转基因小鼠表现出明显的增殖反应。因此，MMPs可能在肿瘤进展中发挥多种作用。
