MOLECULAR-CLONING OF A HUMAN MELANOMA-ASSOCIATED CHONDROITIN SULFATE PROTEOGLYCAN

A human melanoma-associated chondroitin sulfate proteoglycan (MCSP), r ecognized by mAb 9.2.27, plays a role in stabilizing cell-substratum i nteractions during early events of melanoma cell spreading on endothel ial basement membranes. We report here the molecular cloning and nucle otide sequencing of cDNA encoding the entire core protein of human MCS P and provide its deduced amino acid sequence, This core protein conta ins an open reading frame of 2322 aa, encompassing a large extracellul ar domain, a hydrophobic transmembrane region, and a relatively short cytoplasmic tail, Northern blot analysis indicated that MCSP cDNA prob es detect a single 8.0-kb RNA species expressed in human melanoma cell lines, In situ hybridization experiments with a segment of the MCSP c oding sequence localized MCSP mRNA in biopsies prepared from melanoma skin metastases. Multiple human Northern blots with an MCSP-specific p robe revealed a strong hybridization signal only with melanoma cells a nd not with other human cancer cells or a variety of human fetal and a dult tissues, These data indicate that MCSP represents an integral mem brane chondroitin sulfate proteoglycan expressed by human malignant me lanoma cells, The availability of cDNAs encoding MCSP should facilitat e studies designed to establish correlations between structure and fun ction of this molecule and help to establish its role in the progressi on of human malignant melanoma.