Tumoral and choroidal vascularization: Differential cellular mechanisms involving plasminogen activator inhibitor type 1
Jost, Maud Maillard, Catherine Lecomte, Julie Lambert, Vincent Tjwa, Marc Blaise, Pierre Gonzalez, Maria-Luz Alvarez Bajou, Khalid Blacher, Silvia Motte, Patrick Humblet, Chantal Defresne, Marie Paule Thiry, Marc Frankenne, Francis Gothot, Andre Carmeliet, Peter Rakic, Jean-Marie Foidart, Jean-Michel Noel, Agnbs # ×
Amer soc investigative pathology, inc
American Journal of Pathology vol:171 issue:4 pages:1369-1380
An adequate balance between serine proteases and their plasminogen activator hihibitor-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 wildtype 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.