Tariq Shah1, Flonne wildes1, Venu Raman1, Zaver M. Bhujwalla1
1JHU ICMIC Program, Rusell H. Morgan Department of Radiogy and Radiological Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
The overexpression of VEGF has been associated with tumor progression and poor prognosis in several cancers including breast cancer. VEGF mediates increased microvascular permeability, endothelial cell proliferation, invasion, migration, and survival. In this study we have investigated the invasive properties and metabolism of VEGF165 overexpressing MCF-7 cells using an MR compatible cell perfusion-invasion assay, the Metabolic Boyden Chamber. We observed significant degradation of matrigel by VEGF MCF-7 cells while empty vector (EV) MCF-7 and wild type MCF-7 cells showed negligible degradation. A significant increased lactate levels in VEGF MCF-7 compared to control MCF-7 cells was also observed. The increased lactate production of VEGF MCF-7 cells is consistent with its increased malignancy as increased glycolysis and acidic extracellular pH are associated with a more malignant phenotype. Our data support the possibility that in addition to its known paracrine effects, VEGF can increase invasion and alter metabolism of cancer cells through autocrine signaling, providing additional reasons for targeting this cytokine.
Keywords