Source : Direct Effect of Bevacizumab on Glioblastoma Cell Lines In Vitro

Abstract

 Bevacizumab is a humanized monoclonal antibody directed against the pro-angiogenic factor vascular and endothelial growth factor-A (VEGF-A) used in the treatment of glioblastomas. Although most patients respond initially to this treatment, studies have shown that glioblastomas eventually recur. Several non-mutually exclusive theories based on the anti-angiogenic effect of bevacizumab have been proposed to explain these mechanisms of resistance. In this report, we studied whether bevacizumab can act directly on malignant glioblastoma cells. We observe changes in the expression profiles of components of the VEGF/VEGF-R pathway and in the response to a VEGF-A stimulus following bevacizumab treatment. In addition, we show that bevacizumab itself acts on glioblastoma cells by activating the Akt and Erks survival signaling pathways. Bevacizumab also enhances proliferation and invasiveness of glioblastoma cells in hyaluronic acid hydrogel. We propose that the paradoxical effect of bevacizumab on glioblastoma cells could be due to changes in the VEGF-A-dependent autocrine loop as well as in the intracellular survival pathways, leading to the enhancement of tumor aggressiveness. Investigation of how bevacizumab interacts with glioblastoma cells and the resulting downstream signaling pathways will help targeting populations of resistant glioblastoma cells.


gregory

gregory

Grégory MAUBON is Chief Data Officer and digital coordinator at HCS Pharma, a biotech startup focused in high content screening and complex diseases. He manages IT missions and leads digital usages linked to company needs. He is also a Augmented Reality Evangelist (presenter and lecturer) since 2008, where he created www.augmented-reality.fr and founded in 2010 RA'pro (the augmented reality promotion association). He helped many companies (in several domains) to define precisely their augmented reality needs and supported them in the implementation.

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