| First Author | Lochter A | Year | 1999 |
| Journal | Mol Biol Cell | Volume | 10 |
| Issue | 2 | Pages | 271-82 |
| PubMed ID | 9950676 | Mgi Jnum | J:53052 |
| Mgi Id | MGI:1331237 | Doi | 10.1091/mbc.10.2.271 |
| Citation | Lochter A, et al. (1999) alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression. Mol Biol Cell 10(2):271-82 |
| abstractText | Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits alpha6 and beta1, but not against alpha1 and alpha2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against beta1, but not against alpha6 or alpha2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against alpha1 integrins impaired only cell adhesion to type IV collagen. Antibodies against alpha1, alpha2, alpha6, and beta1, but not alpha5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins alpha1 and alpha2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against alpha1 and alpha2, but not alpha6 and beta1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against alpha1 and alpha2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-alpha6 antibodies. Our data indicate that alpha1 and alpha2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas alpha6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion. |
