| First Author | Abety AN | Year | 2012 |
| Journal | J Invest Dermatol | Volume | 132 |
| Issue | 10 | Pages | 2451-2458 |
| PubMed ID | 22622419 | Mgi Jnum | J:189567 |
| Mgi Id | MGI:5446116 | Doi | 10.1038/jid.2012.153 |
| Citation | Abety AN, et al. (2012) Stromal fibroblast-specific expression of ADAM-9 modulates proliferation and apoptosis in melanoma cells in vitro and in vivo. J Invest Dermatol 132(10):2451-8 |
| abstractText | ADAMs are members of the zinc metalloproteinase superfamily characterized by the presence of disintegrin and metalloprotease domains. In human melanoma, ADAM-9 is expressed in focalized areas of the tumor-stroma border in both melanoma and stromal cells. However, the role of ADAM-9 in melanoma progression remains elusive. To analyze the role of stromal-derived ADAM-9 for the growth and survival of melanoma cells, we have used in vitro coculture systems of melanoma cells and ADAM-9(-/-) fibroblasts. Coculture of melanoma cells in the presence of ADAM-9(-/-) fibroblasts led to increased melanoma cell proliferation and reduced apoptosis as compared with control cocultures. We identified TIMP-1 and sTNFRI as the two relevant factors expressed in increased amounts in culture supernatants from ADAM-9(-/-) fibroblasts. TIMP-1 was associated with induced melanoma cell proliferation, whereas soluble TNFR1 mediated the reduced cellular apoptosis in vitro. In vivo, injection of murine melanoma cells into the flank of ADAM-9(-/-) animals resulted in the development of significantly larger tumors than in wild-type animals as a result of increased proliferation and decreased apoptosis of melanoma cells. Taken together, stromal expression of ADAM-9 during melanoma development modulates the expression of TIMP-1 and sTNFR1, which in turn affect tumor cell proliferation and apoptosis. |
