Title: Tumoral and choroidal vascularization: Differential cellular mechanisms involving plasminogen activator inhibitor type 1
Authors: 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 # ×
Issue Date: Oct-2007
Publisher: Amer soc investigative pathology, inc
Series Title: American Journal of Pathology vol:171 issue:4 pages:1369-1380
Abstract: 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.
ISSN: 0002-9440
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Molecular and Vascular Biology
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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