Polette M, Clavel C, Cockett M, Girod de Bentzmann S, Murphy G, Birembaut P
INSERM U-314, Reims, France.
Invasion Metastasis. 1993;13(1):31-7.
Matrix metalloproteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective-tissue-matrix remodelling and the accelerated breakdown associated with tumor development. These MMPs and tissue inhibitor of MMPs (TIMP1) could be expressed by either the cancer or the stromal cells. Expression of mRNAs encoding interstitial collagenase (MMP1), 72-kD type IV collagenase (MMP2) and stromelysin (MMP3), which are probably involved in tumor invasion and metastasis, and of TIMP1 were studied in human mammary pathology by in situ hybridization and Northern blot analysis. Out of 6 benign lesions, 2 expressed MMP2 mRNAs. mRNAs encoding MMP1 and MMP3 were detectable in occasional stromal and tumor cells in 2 out of 17 carcinomas. Thirteen out of 17 cancers expressed MMP2 mRNA throughout the tumor in stromal cells close to noninvasive tumor clusters and well-differentiated invasive cancer cells. TIMP1 mRNA expression was detected in noninvasive and well-differentiated invasive tumor cells. These data suggest that there is a cooperation between tumor and stromal cells, in particular for the production of 72-kD type IV collagenase, involved in the disruption of basement membranes. A lack of TIMP1 expression from invasive cancer cells would also contribute to matrix destruction.
基质金属蛋白酶（MMPs）是一类酶，被认为既参与正常结缔组织基质重塑，也与肿瘤发展相关的加速破坏过程有关。这些基质金属蛋白酶和基质金属蛋白酶组织抑制剂（TIMP1）可由癌细胞或基质细胞表达。通过原位杂交和Northern印迹分析，研究了在人类乳腺病理学中可能参与肿瘤侵袭和转移的编码间质胶原酶（MMP1）、72-kD IV型胶原酶（MMP2）和基质溶解素（MMP3）的mRNA以及TIMP1的表达情况。在6个良性病变中，2个表达MMP2 mRNA。在17例癌中的2例中，偶尔可在基质细胞和肿瘤细胞中检测到编码MMP1和MMP3的mRNA。17例癌中有13例在靠近非侵袭性肿瘤簇的基质细胞以及高分化侵袭性癌细胞中，整个肿瘤均表达MMP2 mRNA。在非侵袭性和高分化侵袭性肿瘤细胞中检测到TIMP1 mRNA表达。这些数据表明肿瘤细胞与基质细胞之间存在协同作用，特别是在参与基底膜破坏的72-kD IV型胶原酶的产生方面。侵袭性癌细胞中TIMP1表达的缺乏也会导致基质破坏。
