A switch from stromal to tumor cell expression of stromelysin‐1 mRNA associated with the conversion of squamous to spindle carcinomas during mouse skin tumor progression

Abstract

We previously reported that the expression of stromelysin-1 (ST-1), a matrix-degrading metalloproteinase, correlates with tumor progression in the mouse skin model of carcinogenesis. Using in situ hybridization techniques, we confirmed in this study the expression of ST-1 mRNA in mouse skin keratinocytes treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and also observed dramatic expression of ST-1 message in underlying fibroblastic cells. Benign tumors formed by an initiation/promotion protocol expressed low levels of ST-1 mRNA, which was localized exclusively to stromal tissue surrounding the tumor cells. Squamous cell carcinomas, produced either by chemical carcinogenesis or by injection of cultured cells derived from chemically initiated squamous cell tumors, expressed high levels of ST-1 mRNA, which was also localized to adjacent stromal tissues. In contrast, aggressive, highly metastatic spindle cell tumors expressed ST-1 mRNA in the tumor cells as well as in normal, adjacent stroma. These results suggest that the change from ST-1 expression in surrounding stromal cells to its expression in the tumor cells themselves is associated with the conversion of squamous to spindle carcinomas and may play a causal role in the ability of these cells to invade and metastasize.