Paloma Silva de Souza
Instituto Nacional de Cancer, Brazil
Posters & Accepted Abstracts: J Cancer Sci Ther
Glioblastoma (GBM) is the most common astrocytoma and one of the most aggressive and lethal human malignancies. Patients with GBM have a median survival of 12 months. Recurrence and tumor progression are related to chemo- and radioresistance and occurs in the majority of the cases. Numerous mechanisms contribute to GBM resistance, including ABC transporters expression, EGFR amplification, and EGFR mutation such as variant III (EGFRvIII). Studies have shown that these molecules can be identified in circulating microvesicles (MVs) secreted by patients. Here, we isolated MVs from peripheral blood samples obtained from sixteen patients with astrocytomas. Only nine of these samples were confirmed as astrocytomas, three were classified as metastasis, three as oligoastrocitomas and one as oligodendroglioma. Among the cases studied, two patients died. In addition, we analyzed the cellular transformation ability of MVs secreted by GBM cells treated with ionizing radiation (IR) or temozolomide (TMZ) in human fibroblast (HF) cells. Our data showed that MVs secreted by GBM cells were able to carry and transfer EGFR protein to HF cells. Moreover, MVs secreted by IR- or TMZ-treated GBM cells induced highest apoptosis resistance in HF cells than MVs secreted by untreated cells. However, activation of ERK1/2 pathway, determined by phosphorylation of ERK, an increased expression of YB-1 and a greater proliferation index, were prominent in HF cells co-cultured with MVs secreted by IR-treated GBM cells. This study will elucidate the role of MVs on tumorigenesis and chemo- and radioresistance mechanisms, promoting advances on efficacy of GBM patients treatment.
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