[Role of matrix metalloproteinases (MMPs) in tumor invasion and metastasis: serial studies on MMPs and TIMPs].
We have conducted serial studies on the role of matrix metalloproteinases (MMPs), especially MMP-9, in tumor invasion and metastasis. In 9 human carcinoma cell lines derived from lung, prostate and melanoma, we found, by zymography and Western blot, that the expression levels of MMP-2 and MMP-9 correlated well with their invasive as well as metastatic abilities both in vitro and in nude mice. When anti-sense MMP-9 cDNA was introduced into WM451, a highly metastatic human melanoma cell line with high expression level of MMP-9, a significant down-regulation of MMP-9 protein expression was found. Meanwhile, the number of cells passing through Matrigel-coated membrane (in vitro invasion assay) and spontaneous metastases to lymph nodes and lungs were significantly reduced. Furthermore, when tissue inhibitors of metalloproteinases-1, -2 or -3 (TIMP-1, TIMP-2 or TIMP-3) cDNAs were individually transtected into metastatic cancer cells, remarkable inhibition of invasion and metastasis were also noticed in each group. These results demonstrate that either up-regulation of TIMPs or down-regulation of MMPs could significantly inhibit the expression of malignant phenotypes, suggesting the important role MMP-9 plays in tumor invasion and metastasis.
Fang
Weigang
W
Department of Pathology, Peking University School of Basic Medical Sciences, Beijing 100083, China. wgfang@bjmu.edu.cn
Li
Hongmei
H
Kong
Lingling
L
Niu
Guilian
G
Gao
Qing
Q
Zhou
Kexiang
K
Zheng
Jie
J
Wu
Bingquan
B
D000818:Animals; D015536:Down-Regulation; D006801:Humans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008545:Melanoma; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019717:Tissue Inhibitor of Metalloproteinase-3; D015854:Up-Regulation
C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; C088390:TIMP3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9