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The role of VEGF in normal and neoplastic hematopoiesis

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Abstract

VEGF is a secreted growth factor that mediates its biological effects by binding to two transmembrane tyrosine kinase receptors, VEGFR-1 and VEGFR-2. The VEGF/receptor signaling system is involved in the regulation of two fundamental processes in vertebrates: the formation of blood vessels (angiogenesis) and of blood cells (hematopoiesis). Hematopoietic stem cells, capable of giving rise to all blood cell lineages, are often found in clusters with endothelial cells, the key cell type involved in the formation of blood vessels. Despite such proximity of VEGF-responsive cells, hematopoiesis occurs independently of neoangiogenesis in the adult bone marrow, suggesting that VEGF regulates the two processes by different mechanisms. In support of this hypothesis, the recently identified autocrine loop by which VEGF may control hematopoietic stem cell survival and repopulation, is fundamentally different from its paracrine effects regulating angiogenesis. Furthermore, coexpression of VEGF and its receptors, the prerequisite for autocrine loops, is frequently found in lymphomas and myelomas, suggesting that autocrine loops also play a role in hematological malignancies. Several therapeutic strategies blocking VEGF or VEGF-induced signaling are currently being investigated for the treatment of neoplastic diseases. They differ in their potential to interfere with the autocrine or paracrine effector functions of VEGF during angiogenesis, hematopoiesis, and tumor cell proliferation, properties which may ultimately determine their therapeutic potential.

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Abbreviations

EPC:

Endothelial progenitor cell

HPC:

Hematopoietic progenitor cell

HSC:

Hematopoietic stem cell

PlGF:

Placental growth factor

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

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Acknowledgements

We thank Bob Cohen, Ellen Filvaroff and Anja Ruchatz for critical reading of the manuscript and David Wood for excellent graphic artwork.

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  1. Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA

    Hans-Peter Gerber & Napoleone Ferrara

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Correspondence to Hans-Peter Gerber.

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Gerber, HP., Ferrara, N. The role of VEGF in normal and neoplastic hematopoiesis. J Mol Med 81, 20–31 (2003). https://doi.org/10.1007/s00109-002-0397-4

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