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Surface Density of Vascular Endothelial Growth Factor Modulates Endothelial Proliferation and Differentiation
Author(s) -
Galas Richard J.,
Liu Julie C.
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24638
Subject(s) - vascular endothelial growth factor , microbiology and biotechnology , endothelial stem cell , cell growth , vascular endothelial growth factor a , cell , chemistry , cell culture , receptor , growth factor , biology , vegf receptors , cancer research , biochemistry , in vitro , genetics
Therapeutic strategies aim to regulate vasculature either by encouraging vessel growth for tissue engineering or inhibiting vascularization around a tumor. Vascular endothelial growth factor (VEGF) is essential to these processes, and there are several strategies that manipulate VEGF signaling. Here we develop a method to control the surface density of VEGF, which is covalently attached to tissue culture polystyrene (TCPS), and explore cellular responses to surfaces with varying VEGF densities. We show that the crosslinker reduces but does not eliminate the biological activity of soluble VEGF as measured by endothelial proliferation. However, endothelial cells cultured on surfaces of covalently bound VEGF did not proliferate in response to surface cues. Interestingly, compared to cells incubated with soluble VEGF (10 ng/ml) and cultured on TCPS, lower cell proliferation was observed when endothelial cells were cultured on high VEGF surface densities (5.9 ng/cm 2 ), whereas higher cell proliferation occurred when cells were cultured on low surface densities (0.04 ng/cm 2 ). High density surfaces (5.9 ng/cm 2 ) also acted in synergy with an inhibitor of VEGF receptors to further suppress endothelial cell proliferation. We also examined the effect of VEGF surfaces on endothelial differentiation of mesenchymal stem cells. No effect was observed when cells were cultured on VEGF surfaces; however, the VEGF surfaces acted in synergy with an inhibitor of VEGF receptors to decrease the ability of differentiated cells to form vascular networks. Together, these results suggest that surface density of bound VEGF can be used to modulate cell behavior and inhibit an angiogenic response. J. Cell. Biochem. 115: 111–120, 2014. © 2013 Wiley Periodicals, Inc.