Okada A, Bellocq J P, Rouyer N, Chenard M P, Rio M C, Chambon P, Basset P
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.
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2730-4. doi: 10.1073/pnas.92.7.2730.
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.
从乳腺癌cDNA文库中，我们克隆了一些cDNA，这些cDNA被证明与最近在人胎盘中发现的膜型基质金属蛋白酶（MT-MMP）相对应，并被认为是前明胶酶A的激活剂[Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E. & Seiki, M. (1994) Nature (London) 370, 61 - 65]。用其中一个cDNA作为探针，我们通过RNA原位杂交在所有检测的83个人类癌组织标本中检测到了MT-MMP基因的表达，并在肿瘤基质的成纤维细胞中发现了MT-MMP转录本，但在癌细胞中未发现。与在人类癌组织的成纤维细胞中表达的其他MMP基因进行比较表明，MT-MMP基因的表达模式与明胶酶A基因的表达模式比与基质溶解素3或间质胶原酶基因的表达模式更为密切相关。这些观察结果与MT-MMP和明胶酶A在肿瘤进展过程中协同作用的假设一致，并强化了源自人类癌组织基质成分的蛋白水解活性在肿瘤进展中起关键作用的概念。
