Abstract

Malignant gliomas are the leading cause of central nervous system (CNS) tumor-related death. The failure of conventional cancer therapeutics results from the aberrant angiogenesis in gliomas. Abnormal vessel structure of gliomas, resulting in decreased delivery of chemotherapies, increased tumor hypoxia and edema leading to further complications. In this study, role of the nucleotide-binding domain, leucine rich containing (NLR) proteins in glioblastoma angiogenesis is studied. Some NLR proteins form a multi-protein complex with procaspase-1, called the “inflammasome”. Aberrant angiogenesis with torturous and leaky vessels and hypoxic core are the hallmarks of glioblastoma. Glioblastoma consists of heterogeneous population of cells such as microglial, endothelial cells, astrocytes, neurons and stromal cells. These characteristics of glioblastoma make them resistant to conventional therapy thereby decreasing the overall survival of glioblastoma patients. Therefore knowledge of NLR expression in different cell population within glioblastoma becomes essential. Also, the variation in the expression pattern in these cells within hypoxia and normoxia needs to be explored. The contribution of NLRs to glioma angiogenesis was also investigated. This cell specific expression profiling of NLRs in gliomas and their role in glioma angiogenesis is necessary for generation of novel therapeutic interventions. Gene and protein expression of inflammasome forming NLRs in Human Umbilical Vein Endothelial Cells (HUVEC) with respect to gliomas under normoxic and hypoxic conditions has been characterized. It was observed that NLRs are expressed in LN18 and A172 glioblastoma cells and also in HUVECs and their expression varies under inflammation as well as hypoxic conditions. Expression profiling of NLRs under hypoxia varies in an opposite manner between glioblastoma cells and microglial cells. NLRP12 is observed to play an essential role in the glioblastoma growth and development. This research will pave the way for development of effective immunity and angiogenesis directed cancer therapies.

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