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Human head and neck squamous cell carcinoma cells are both targets and effectors for the angiogenic cytokine, VEGF
Author(s) -
Tong Meng,
Lloyd Brandon,
Pei Ping,
Mallery Susan R.
Publication year - 2008
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.21920
Subject(s) - head and neck squamous cell carcinoma , cancer research , angiogenesis , vascular endothelial growth factor , cytokine , vascular endothelial growth factor a , transfection , biology , cell culture , chemistry , cancer , medicine , immunology , vegf receptors , head and neck cancer , genetics
Former vascular endothelial growth factor (VEGF)–head and neck squamous cell carcinoma (HNSCC) studies have focused on VEGF's contributions toward tumor‐associated angiogenesis. Previously, we have shown that HNSCC cells produce high levels of VEGF. We therefore hypothesized that VEGF serves a biphasic role, that is, pro‐angiogenic and pro‐tumorigenic in HNSCC pathogenesis. Western blots confirmed the presence of VEGF's primary mitogenic receptors, VEGFR‐2/KDR and VEGFR‐1/Flt‐1 in cultured HNSCC cells. Subsequent studies evaluated VEGF's effects on HNSCC intracellular signaling, mitogenesis, invasive capacities, and matrix metalloproteinases (MMPs) activities. Introduction of hr VEGF 165 initiated ROS‐mediated intracellular signaling, resulting in kinase activation and phosphorylation of KDR and Erk1/2. As high endogenous VEGF production rendered HNSCC cells refractory to exogenous VEGF's mitogenic effects, siRNA was employed, inhibiting endogenous VEGF production for up to 96 h. Relative to transfection vector matched controls, siRNA treated HNSCC cells showed a significant decrease in proliferation at both 30 and 50 nM siRNA doses. Addition of exogenous hr VEGF 165 (30 and 50 ng/ml) to siRNA‐silenced HNSCC cells resulted in dose‐dependent increases in cell proliferation. Cell invasion assays showed VEGF is a potent HNSCC chemoattractant and demonstrated that VEGF pre‐treatment enhanced invasiveness of HNSCC cells. Conditioned media from VEGF challenged HNSCC cells showed a moderate increase in gelatinase activity. Our results demonstrate, for the first time, that HNSCC cells are both targets and effectors for VEGF. These data introduce the prospect that VEGF targeted therapy has the potential to fulfill both anti‐angiogenic and anti‐tumorigenic functions. J. Cell. Biochem. 105: 1202–1210, 2008. © 2008 Wiley‐Liss, Inc.