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Full-Text Articles in Medicine and Health Sciences

Exosomes Secreted Under Hypoxia Enhance Stemness In Ewing's Sarcoma Through Mir-210 Delivery, Matthew J. Kling, Nagendra K. Chaturvedi, Varun Kesherwani, Don W. Coulter, Timothy R. Mcguire, J. Graham Sharp, Shantaram S. Joshi Oct 2020

Exosomes Secreted Under Hypoxia Enhance Stemness In Ewing's Sarcoma Through Mir-210 Delivery, Matthew J. Kling, Nagendra K. Chaturvedi, Varun Kesherwani, Don W. Coulter, Timothy R. Mcguire, J. Graham Sharp, Shantaram S. Joshi

Journal Articles: Genetics, Cell Biology & Anatomy

Intercellular communication between tumor cells within the hypoxic microenvironment promote aggressiveness and poor patient prognoses for reasons that remain unclear. Here we show that hypoxic Ewing's sarcoma (EWS) cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival. Analysis of the hypoxic exosomal miRNA cargo identified a HIF-1α regulated miRNA, miR-210, as a potential mediator of sphere formation in cells exposed to hypoxic exosomes. Knockdown of HIF-1α in hypoxic EWS cells led to decreased exosomal miR-210 levels and reduced the capacity of hypoxic exosomes to form spheres. Inhibition of miR-210 in hypoxic spheres attenuated …


Exosomes Secreted Under Hypoxia Enhance Stemness In Ewing’S Sarcoma And Transform Microenvironment Cells, Matthew J. Kling Aug 2020

Exosomes Secreted Under Hypoxia Enhance Stemness In Ewing’S Sarcoma And Transform Microenvironment Cells, Matthew J. Kling

Theses & Dissertations

Intercellular communication between tumor cells and stroma within the hypoxic microenvironment promote aggressiveness and poor patient prognoses in ways that remain unclear. Here we show that hypoxic Ewing’s sarcoma (EWS) cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival and a cancer-associated phenotype in fibroblasts (CAFs). Given that hypoxia enriches for stem-like cells, we exposed EWS cells to hypoxia and hypoxic EWS-derived exosomes and assessed the stem cell phenotype. Hypoxia and hypoxic EWS-derived exosomewere found to enhance TIC formation in vitro and in vivo by reprogramming EWS cells. Analysis of the hypoxic exosomal …