| First Author | Abraham V | Year | 2018 |
| Journal | Int J Oncol | Volume | 53 |
| Issue | 2 | Pages | 488-502 |
| PubMed ID | 29845213 | Mgi Jnum | J:309812 |
| Mgi Id | MGI:6760481 | Doi | 10.3892/ijo.2018.4422 |
| Citation | Abraham V, et al. (2018) Involvement of TIMP-1 in PECAM-1-mediated tumor dissemination. Int J Oncol 53(2):488-502 |
| abstractText | Platelet endothelial cell adhesion molecule1 (PECAM1) is expressed on the vascular endothelium and has been implicated in the late progression of metastatic tumors. The activity of PECAM1 appears to be mediated by modulation of the tumor microenvironment (TME) and promotion of tumor cell proliferation, rather than through the stimulation of tumor angiogenesis. The present study aimed to extend those initial findings by indicating that the presence of functional PECAM1 on the endothelium promotes a proliferative tumor cell phenotype in vivo, as well as in tumor cell (B16F10 melanoma and 4T1 breast cancer cell lines) coculture assays with mouse endothelial cells (ECs) or a surrogate EC line (RENMP). The proproliferative effects were mediated by soluble endothelialderived factors that were dependent on PECAM1 homophilic ligand interactions, but which were independent of PECAM1dependent signaling. Further analysis of the conditioned media obtained from tumor/EC and tumor/RENMP cocultures identified TIMP metallopeptidase inhibitor1 (TIMP1) as a PECAM1regulated factor, the targeting of which in the tumor cell/RENMP system inhibited tumor cell proliferation. In addition, TIMP1 expression was decreased in metastatic tumors from the lungs of PECAM1null mice, thus providing evidence of the in vivo significance of coculture studies. Taken together, these studies indicated that endothelial PECAM1, through PECAM1dependent homophilic binding interactions, may induce release of TIMP1 from the endothelium into the TME, thus leading to increased tumor cell proliferation. |
