| First Author | Jost M | Year | 2007 |
| Journal | Am J Pathol | Volume | 171 |
| Issue | 4 | Pages | 1369-80 |
| PubMed ID | 17717143 | Mgi Jnum | J:125522 |
| Mgi Id | MGI:3759001 | Doi | 10.2353/ajpath.2007.070074 |
| Citation | Jost M, et al. (2007) Tumoral and choroidal vascularization: differential cellular mechanisms involving plasminogen activator inhibitor type I. Am J Pathol 171(4):1369-80 |
| abstractText | An adequate balance between serine proteases and their plasminogen activator inhibitor-1 (PAI-1) is critical for pathological angiogenesis. PAI-1 deficiency in mice is associated with impaired choroidal neovascularization (CNV) and tumoral angiogenesis. In the present work, we demonstrate unexpected differences in the contribution of bone marrow (BM)-derived cells in these two processes regulated by PAI-1. PAI-1(-/-) mice grafted with BM-derived from wild-type mice were able to support laser-induced CNV formation but not skin carcinoma vascularization. Engraftment of irradiated wild-type mice with PAI-1(-/-) BM prevented CNV formation, demonstrating the crucial role of PAI-1 delivered by BM-derived cells. In contrast, the transient infiltration of tumor transplants by local PAI-1-producing host cells rather than by BM cells was sufficient to rescue tumor growth and angiogenesis in PAI-1-deficient mice. These data identify PAI-1 as a molecular determinant of a local permissive soil for tumor angiogenesis. Altogether, the present study demonstrates that different cellular mechanisms contribute to PAI-1-regulated tumoral and CNV. PAI-1 contributes to BM-dependent choroidal vascularization and to BM-independent tumor growth and angiogenesis. |
