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) recently identified in human placenta and proposed to be an activator of progelatinase 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 expression in all 83 human carcinoma specimens examined by RNA in situ hybridization and have found MT-MMP transcripts in fibroblastic cells of tumor stroma but not in cancer cells. Comparison with other MMP genes expressed in fibroblastic cells of human carcinomas indicated that the expression 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 interstitial collagenase genes. These observations are consistent with the hypothesis that MT-MMP and gelatinase A are cooperating during tumor progression and strengthen the concept that proteolytic activities originating from the stromal component of human carcinomas have a critical role in tumor progression.
Okada
A
A
Institut de Génétique et de Biologie Moléculaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur/Collège de France, Illkirch.
Bellocq
J P
JP
Rouyer
N
N
Chenard
M P
MP
Rio
M C
MC
Chambon
P
P
Basset
P
P
D000230:Adenocarcinoma / Q000201:enzymology; D000236:Adenoma / Q000201:enzymology; D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology*; D002277:Carcinoma / Q000201:enzymology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D018076:DNA, Complementary; D005260:Female; D018226:Fibroadenoma / Q000201:enzymology; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D017403:In Situ Hybridization; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases