Fibroblasts surrounding melanoma express elevated levels of matrix metalloproteinase-1 (MMP-1) and intercellular adhesion molecule-1 (ICAM-1) in vitro

Tumour growth and metastasis involve the degradation of extracellular matri x components by matrix degrading enzymes produced by tumour cells and strom al fibroblasts. In this study, fibroblasts were obtained from biopsies on t he border (TB) and 1 cm distant from the melanoma (TD) and cultured separat ely. Similar studies were performed with fibroblasts surrounding melanocyti c nevi as control. The expression of matrix metalloproteinase-1 (MMP-1) mRN A and tissue matrix metalloproteinase inhibitor 1 (TIMP-1) were studied by Northern blot analysis. The activation antigen intercellular adhesion molec ule-1 (ICAM-1) in TB- and TD-fibroblasts was investigated by flow cytometry . In melanoma, TB-fibroblasts showed an increased expression of MMP-1 mRNA mainly in fibroblasts obtained from tumours with extended invasive growth d emonstrated by Clark level whereas the expression of the major specific inh ibitor TIMP-1 was unaltered. In contrast, fibroblasts surrounding benign me lanocytic nevi did not express elevated levels of MMP-1. The upregulation o f MMP-1 in TB-fibroblasts compared to TD-fibroblasts was maintained during cultivation. Furthermore, MMP-1 mRNA expression and MMP-1 total protein amo unt in normal fibroblasts were increased by melanoma cell conditioned mediu m. We demonstrated an increased expression of ICAM-1 in TB-fibroblasts comp ared to TD-fibroblasts in vitro depending on the amount of inflammatory inf iltrate in situ. The differences of ICAM expression disappeared during cont inued cell culture. These results support the idea that fibroblasts surroun ding melanoma are activated and are possibly involved in the degradation of matrix proteins surrounding the tumour.