| First Author | Fanjul-Fernández M | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 20 | Pages | 14647-56 |
| PubMed ID | 23548910 | Mgi Jnum | J:198586 |
| Mgi Id | MGI:5498428 | Doi | 10.1074/jbc.M112.439893 |
| Citation | Fanjul-Fernandez M, et al. (2013) Matrix metalloproteinase Mmp-1a is dispensable for normal growth and fertility in mice and promotes lung cancer progression by modulating inflammatory responses. J Biol Chem 288(20):14647-56 |
| abstractText | Human MMP-1 is a matrix metalloproteinase repeatedly associated with many pathological conditions, including cancer. Thus, MMP1 overexpression is a poor prognosis marker in a variety of advanced cancers, including colorectal, breast, and lung carcinomas. Moreover, MMP-1 plays a key role in the metastatic behavior of melanoma, breast, and prostate cancer cells. However, functional and mechanistic studies on the relevance of MMP-1 in cancer have been hampered by the absence of an in vivo model. In this work, we have generated mice deficient in Mmp1a, the murine ortholog of human MMP1. Mmp1a(-/-) mice are viable and fertile and do not exhibit obvious abnormalities, which has facilitated studies of cancer susceptibility. These studies have shown a decreased susceptibility to develop lung carcinomas induced by chemical carcinogens in Mmp1a(-/-) mice. Histopathological analysis indicated that tumors generated in Mmp1a(-/-) mice are smaller than those of wild-type mice, consistently with the idea that the absence of Mmp-1a hampers tumor progression. Proteomic analysis revealed decreased levels of chitinase-3-like 3 and accumulation of the receptor for advanced glycation end-products and its ligand S100A8 in lung samples from Mmp1a(-/-) mice compared with those from wild-type. These findings suggest that Mmp-1a could play a role in tumor progression by modulating the polarization of a Th1/Th2 inflammatory response to chemical carcinogens. On the basis of these results, we propose that Mmp1a knock-out mice provide an excellent in vivo model for the functional analysis of human MMP-1 in both physiological and pathological conditions. |
