Matrix Metalloproteinases Contribute Distinct Roles in Neuroendocrine Prostate Carcinogenesis, Metastasis, and Angiogenesis Progression

摘要: Prostate cancer is the leading form of in men. tumors often contain neuroendocrine differentiation, which correlates with androgen-independent progression and poor prognosis. Matrix metalloproteinases (MMP), a family enzymes that remodel microenvironment, are associated tumorigenesis metastasis. To evaluate MMPs during metastatic prostatic development, we used transgenic mice expressing SV40 large T antigen their cells, under control transcriptional regulatory elements from mouse cryptdin-2 gene (CR2-TAg). These have stereotypical pattern MMP-2, MMP-7, MMP-9 activities increased concurrently transition to invasive carcinoma, but they were expressed different cell types: stromal, luminal epithelium, macrophages, respectively. CR2-TAg treated AG3340/Prinomastat, an MMP inhibitor blocks activity MMP-9, MMP-13, MMP-14, had reduced tumor burden. animals crossed homozygous for null alleles or genes. At 24 weeks CR2-TAg; MMP-2−/− showed burden, prolonged survival, decreased lung metastasis, blood vessel density, whereas deficiencies MMP-7 did not influence growth survival. Mice deficient endothelial area coverage size, lacking numbers foci perivascular invasion, as well size. Together, these results suggest distinct contributions by aggressive prostate helping cleverly find alternative routes malignant progression. Cancer Res; 70(6); 2224–34