HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Summary Full Text Full Text (PDF) All Versions of this Article: fj.05-5137fjev1 20/9/1495    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, B. Articles by Young, P. P. Search for Related Content PubMed PubMed Citation Articles by Li, B. Articles by Young, P. P.

VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization

Bin Li^*, Emerson E. Sharpe^*, Amanda B. Maupin^*, Amylynn A. Teleron^*, Amy L. Pyle^*, Peter Carmeliet and Pampee P. Young^*,,1

Departments of
^* Pathology and

Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; and

Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium

¹Correspondence: Vanderbilt University School of Medicine, Department of Pathology, 1161 21st Ave. South, C2217 MCN, Nashville, TN 37232. E-mail: pampee.young{at}vanderbilt.edu

ABSTRACT

There are growing data to suggest that tissue hypoxia represents a critical force that drives adult vasculogenesis. Vascular endothelial growth factor (VEGF) expression is dramatically up-regulated by hypoxia and results in enhanced neovascularization. Although the role of VEGF in angiogenesis has been well characterized, its role in adult vasculogenesis remains poorly understood. We used two distinct murine bone marrow transplantation (BMT) models to demonstrate that increased VEGF levels at the site of tumor growth promoted vasculogenesis in vivo. This effect of VEGF was downstream of its effect to enhance either mobilization or survival of circulating endothelial progenitor cells (EPCs). Both VEGFR1 (flt1) and VEGFR2 (flk1) are expressed on culture expanded human EPCs. Previous studies suggest that the effect of VEGF on endothelial cell migration is primarily mediated via VEGFR2; however, VEGF-induced EPC migration in vitro was mediated by both receptors, suggesting that VEGF-VEGFR1 interactions in EPCs are distinct from differentiated endothelial cells. We used specific blocking antibodies to these receptors to demonstrate that VEGFR1 plays an important role in human EPC recruitment to tumors. These findings were further supported by our finding that tumor-associated placental growth factor (PlGF), a VEGFR1-specific agonist, increased tumor vasculogenesis in a murine BMT model. We further showed that both VEGF receptors were necessary for the formation of functional vessels derived from exogenously administered human ex vivo expanded EPCs. Our data suggest local VEGF and/or PlGF expression promote vasculogenesis; VEGF plays a role in EPC recruitment and subsequent formation of functional vessels.—Li, B., Sharpe, E. E., Maupin, A., Teleron, A. A., Pyle, A., Carmeliet, P., Young, P. P. VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization.

This article has been cited by other articles:

				C. G. Peralta, V. K. Han, J. Horrocks, B. A. Croy, and M. J. van den Heuvel CD56bright cells increase expression of {alpha}4 integrin at ovulation in fertile cycles J. Leukoc. Biol., October 1, 2008; 84(4): 1065 - 1074. [Abstract] [Full Text] [PDF]

				S. Takaishi, T. Okumura, and T. C. Wang Gastric Cancer Stem Cells J. Clin. Oncol., June 10, 2008; 26(17): 2876 - 2882. [Abstract] [Full Text] [PDF]

				S. Mieno, R. T. Clements, M. Boodhwani, N. R. Sodha, B. Ramlawi, C. Bianchi, and F. W. Sellke Characteristics and Function of Cryopreserved Bone Marrow-Derived Endothelial Progenitor Cells Ann. Thorac. Surg., April 1, 2008; 85(4): 1361 - 1366. [Abstract] [Full Text] [PDF]

				R. Ria, C. Piccoli, T. Cirulli, F. Falzetti, G. Mangialardi, D. Guidolin, A. Tabilio, N. Di Renzo, A. Guarini, D. Ribatti, et al. Endothelial Differentiation of Hematopoietic Stem and Progenitor Cells from Patients with Multiple Myeloma Clin. Cancer Res., March 15, 2008; 14(6): 1678 - 1685. [Abstract] [Full Text] [PDF]

				J. Wels, R. N. Kaplan, S. Rafii, and D. Lyden Migratory neighbors and distant invaders: tumor-associated niche cells Genes & Dev., March 1, 2008; 22(5): 559 - 574. [Abstract] [Full Text] [PDF]

				J. B. Ray, S. Arab, Y. Deng, P. Liu, L. Penn, D. W. Courtman, and M. E. Ward Oxygen regulation of arterial smooth muscle cell proliferation and survival Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H839 - H852. [Abstract] [Full Text] [PDF]

				W. B. Slayton, X.-M. Li, J. Butler, S. M. Guthrie, M. L. Jorgensen, J. R. Wingard, and E. W. Scott The Role of the Donor in the Repair of the Marrow Vascular Niche Following Hematopoietic Stem Cell Transplant Stem Cells, November 1, 2007; 25(11): 2945 - 2955. [Abstract] [Full Text] [PDF]

				A. Schmidt, K. Brixius, and W. Bloch Endothelial Precursor Cell Migration During Vasculogenesis Circ. Res., July 20, 2007; 101(2): 125 - 136. [Abstract] [Full Text] [PDF]

				R. T. P. Poon, C. Lau, R. Pang, K. K. Ng, J. Yuen, and S. T. Fan High Serum Vascular Endothelial Growth Factor Levels Predict Poor Prognosis after Radiofrequency Ablation of Hepatocellular Carcinoma: Importance of Tumor Biomarker in Ablative Therapies Ann. Surg. Oncol., June 1, 2007; 14(6): 1835 - 1845. [Abstract] [Full Text] [PDF]

				N. F. Voelkel, I. S. Douglas, and M. Nicolls Angiogenesis in Chronic Lung Disease Chest, March 1, 2007; 131(3): 874 - 879. [Abstract] [Full Text] [PDF]

				S. Nguyen Huu, M. Oster, S. Uzan, F. Chareyre, S. Aractingi, and K. Khosrotehrani Maternal neoangiogenesis during pregnancy partly derives from fetal endothelial progenitor cells PNAS, February 6, 2007; 104(6): 1871 - 1876. [Abstract] [Full Text] [PDF]