Role of NLRs in Glioma Microenvironment.
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Date
2019-07
Researcher
Saxena, Shivanjali
Supervisor
Jha, Sushmita
Journal Title
Journal ISSN
Volume Title
Publisher
Indian Institute of Technology Jodhpur
Abstract
Gliomas are tumors of the Central Nervous System (CNS) that arise from cells of “glial” origin. They account for around 30% of the tumors of the CNS. They are composed of either heterogeneous or homogenous populations of glial cells such as microglia, astrocytes and oligodendrocytes. The growth of tumor leads to increased metabolic demand that creates an environment of low oxygen in the tumor tissue that is termed as “hypoxia”. Hypoxia is a major hallmark of solid umors. It not only supports tumor growth but also helps in proliferation and metastasis. Due to enhanced metabolism nutrient demand also increases. This leads to the secretion of certain factors that initiate the process of formation of new lood vessels termed as “angiogenesis”. Hypoxia is a major player here as it causes the transcription of angiogenic factors such as VEGF, FGF etc. through HIF-1α and leads to angiogenesis. Hypoxia contributes to radio and chemo ozolomide) resistance of tumors causing hindrance to treatment. Hypoxia is known to contribute not only to angiogenesis but is also connected to innate immune system through various transcription factors such as NF-κB, AP-1 etc. Also it is reported to up regulate the expression of various cytokines such as IL-1β and IL-18. Upstream of these cytokines are Nod-like receptors (NLRs). They are the type of innate immune system receptors that get activated in response to various pathogen associated molecular patterns (PAMPs) and danger associated molecular patterns (DAMPs). Role of NLRs in glioma microenvironment remains unexplored. In this work expression of NLRs is assessed in normal versus glioma tissue. As glioma onsists of heterogeneous population of cells, cell specific expression analysis of NLRs is also done. Role of NLRP12 is further explored in glioma growth and invasion. NLRP12 regulates NF-KB activation therefore cell-specific ontribution of hypoxia to NF-kB activation is also analysed. Differential expression of NLRs in glioma and in normal cell lines is observed. NLRP12 is observed as prognostic marker for glioma. NLRP12 positively regulates glioma by contributing to ts growth and invasion inducing ability. Hypoxia positively regulates NLRP12 in glioma cells while negative regulation is observed in microglial cells thereby contributing to glioma development.
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Citation
Saxena, Shivanjali. (2019). Role of NLRs in Glioma Microenvironment (Doctor's thesis). Indian Institute of Technology Jodhpur, Jodhpur.