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VEGF‐R2 and neuropilin‐1 are involved in VEGF‐A‐induced differentiation of human bone marrow progenitor cells
Author(s) -
Fons Pierre,
Herault JeanPascal,
Delesque Nathalie,
Tuyaret Joēl,
Bono Françoise,
Herbert JeanMarc
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20076
Subject(s) - neuropilin 1 , vascular endothelial growth factor , angiogenesis , microbiology and biotechnology , progenitor cell , bone marrow , biology , cancer research , cellular differentiation , stem cell , immunology , biochemistry , vegf receptors , gene
Abstract Tumor growth and metastasis require the generation of new blood vessels, a process known as neo‐angiogenesis. Recent studies have indicated that early tumor vascularization is characterized by the differentiation and mobilization of human bone marrow cells. Vascular endothelial growth factor‐A (VEGF‐A) is one of the growth factors, which enhances their differentiation into endothelial cells, but little is known about the implication of the VEGF‐receptor tyrosine kinases and about the implication of the VEGF‐R co‐receptor, neuropilin‐1, in this process. In this context, the identification of the molecular pathways that support the proliferation and differentiation of vascular stem and progenitor cells was investigated in order to define the pharmaceutical targets involved in tissue vascularization associated with this process. For this purpose, an in vitro model of differentiation of human bone marrow AC133 + (BM‐AC133 + ) cells into vascular precursors was used. In this work, we have demonstrated for the first time that the effect of VEGF‐A on BM‐AC133 + cells relies on an early action of VEGF‐A on the expression of its tyrosine kinase receptors followed by an activation of a VEGF‐R2/neuropilin‐1‐dependent signaling pathway. This signaling promotes the differentiation of BM‐AC133 + cells into endothelial precursor cells, followed by the proliferation of these differentiated cells. Altogether, these results strongly suggest that VEGF inhibitors, acting at the level of VEGF‐R2 and/or neuropilin‐1, by inhibiting differentiation and proliferation of these cells, could be potentially active compounds to prevent progenitor cells to be involved in tumor angiogenesis leading to tumor growth. © 2004 Wiley‐Liss, Inc.