MEMBRANE-TYPE MATRIX METALLOPROTEINASE (MT-MMP) GENE IS EXPRESSED IN STROMAL CELLS OF HUMAN COLON, BREAST, AND HEAD AND NECK CARCINOMAS

From breast cancer cDNA libraries,we have cloned cDNAs that proved to correspond to the membrane-type matrix metalloproteinase (MT-MMP) rece ntly identified in human placenta and proposed to be an activator of p ro-gelatinase A [Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E. & Seiki, M. (1994) Nature (London) 370, 61-65]. Using one of these cDNAs as a probe, we have detected MT-MMP gene expressio n in all 83 human carcinoma specimens examined by RNA in situ hybridiz ation and have found MT-MMP transcripts in fibroblastic cells of tumor stroma but not in cancer cells. Comparison with other MMP genes expre ssed in fibroblastic cells of human carcinomas indicated that the expr ession pattern of the MT-MMP gene was more closely related to that of the gelatinase A gene than to those of the stromelysin 3 or interstiti al collagenase genes. These observations are consistent with the hypot hesis that MT-MMP and gelatinase A are cooperating during tumor progre ssion and strengthen the concept that proteolytic activities originati ng from the stromal component of human carcinomas have a critical role in tumor progression.