Tumoral and choroidal vascularization: differential cellular mechanisms involving plasminogen activator inhibitor type I |
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| Authors: | Jost Maud Maillard Catherine Lecomte Julie Lambert Vincent Tjwa Marc Blaise Pierre Alvarez Gonzalez Maria-Luz Bajou Khalid Blacher Silvia Motte Patrick Humblet Chantal Defresne Marie Paule Thiry Marc Frankenne Francis Gothot André Carmeliet Peter Rakic Jean-Marie Foidart Jean-Michel Noël Agnès |
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| Affiliation: | Laboratory of Tumor and Developmental Biology, University of Liège, Tour de Pathologie, CHU (B23), Sart Tilman; B-4000 Liège, Belgium. |
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| Abstract: | 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. |
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