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Von Hippel Lindau negative tumor cell-derived exosomes in metastatic kidney cancer

Abstract

Metastatic Renal Cell Carcinoma(RCC) has limited safe and effective treatments available. This is due to a lack of understanding relating to the mechanism of distant cancer metastasis. Metastatic crosstalk occurs between pseudo-hypoxic von Hippel-Lindau(VHL) knockout tumor cells and VHL wildtype tumor cells. VHL knockout cells have increased production of exosomes due to their pseudo-hypoxic state to help cells adapt to hypoxic conditions. VHL knockout-derived exosomes increase the metastatic properties of VHL wildtype recipient cells. Metastatic properties such as migration and metastasis occur in response between isolated exosomes from the CRISPR modified VHL(-) Renca murine line and VHL(+) cells, generating a model of RCC metastasis and the potential to develop targeted diagnostics and therapeutics for metastatic disease.

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