INCREASED EXPRESSION OF STROMELYSIN-3 IN BASAL-CELL CARCINOMAS

We examined the expression of two groups of matrix metalloproteinases (MMPs), stromelysin and interstitial collagenase, in human skin cancer by northern blot analysis and in situ hybridization. Stromelysin-3 (S T-3) mRNA was overexpressed more than tenfold in 17 of 19 (89%) specim ens of basal cell carcinoma (BCC) but in only three of 13 (23%) cutane ous squamous cell carcinomas (SCCs). Stromelysin-l and -2 (ST-1/2) mRN A was overexpressed in three of 19 (16%) BCC and three of 13 (23%) SCC . Collagenase mRNA was overexpressed in nine of 19 (47%) BCC and three of 13 (23%) SCC. No mRNA for ST-3, ST-1/2, or collagenase was detecte d by northern ana lysis in 21 specimens of adjacent normal skin. Becau se of these findings, we examined the specific location of the ST-3 mR NA in BCC specimens by in situ hybridization. ST-3 mRNA was particular ly abundant in the characteristic stroma adjacent to the invasive basa loid tumor islands of the BCC and absent in the malignant cells. Moreo ver, ST-3 mRNA was expressed and induced by phorbol ester treatment in adult dermal fibroblasts but not in keratinocytes. In vitro studies h ave shown that MMPs are involved in the degradation of extracellular m atrix molecules. Our finding of ST-3 mRNA overexpression in 17 of 19 ( 89%) BCC specimens is consistent with a role for this molecule in loca l invasion of stroma by BCC. Our in situ hybridization data suggested that while ST-3 is not expressed by malignant basal cells themselves, these tumor cells may induce the expression of ST-3 in adjacent nonmal ignant stromal elements such as fibroblasts. (C) 1994 Wiley-Liss, Inc.