HUMAN KERATINOCYTES EXPRESS EMMPRIN, AN EXTRACELLULAR-MATRIX METALLOPROTEINASE INDUCER

Increased levels of matrix metalloproteinases are associated with tiss ue degradation and remodeling during tumor invasion and wound healing, In both processes, there is evidence that cell interactions between f ibroblasts and tumor cells or keratinocytes lead to increases in metal loproteinase production, We have previously isolated and purified a tu mor cell surface protein, EMMPRIN (extracellular matrix metalloprotein ase inducer), which stimulates production of interstitial collagenase, gelatinase A, and stromelysin-1 by fibroblasts, and we have obtained cDNA clones that encode the EMMPRIN protein from LX-1 human lung carci noma cells, In this study we report immunolocalization of EMMPRIN arou nd the surface of human keratinocytes in vitro and in vivo, and isolat ion of cDNAs that encode the entire open reading frame for EMMPRIN fro m a human keratinocyte library, Comparison of the EMMPRIN cDNAs from n ormal human keratinocytes and LX-1 human turner cells by nucleotide se quence analysis, expression of the recombinant proteins, and in vitro translation using the cDNAs from the two sources indicate that they ex press very similar forms of EMMPRIN, Native EMMPRIN isolated directly from extracts of keratinocytes, however, is slightly smaller in size a nd is present at a lower concentration compared with that from LX-1 tu mor cells, These results establish the presence of EMMPRIN in the norm al epidermis and raise the possibility of its involvement in regulatio n of matrix remodeling at the epidermal-dermal interface.