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Article ; Online: Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma

Kailey Flora / Moe Ishihara / Zhicheng Zhang / Elizabeth S. Bowen / Aimee Wu / Tala Ayoub / Julian Huang / Celine Cano-Ruiz / Maia Jackson / Kaveeya Reghu / Yasmeen Ayoub / Yazhen Zhu / Hsian-Rong Tseng / Z. Hong Zhou / Junhui Hu / Lily Wu

International Journal of Molecular Sciences, Vol 24, Iss 24, p

2023  Volume 17307

Abstract: Exosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the von Hippel-Lindau (VHL) tumor suppressor gene and those that do not is instrumental to distant ... ...

Abstract Exosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the von Hippel-Lindau (VHL) tumor suppressor gene and those that do not is instrumental to distant metastasis in renal cell carcinoma (RCC). In a novel metastasis model, VHL(−) cancer cells are the metastatic driver, while VHL(+) cells receive metastatic signals from VHL(−) cells and undergo aggressive transformation. This study investigates whether exosomes could be mediating metastatic crosstalk. Exosomes isolated from paired VHL(+) and VHL(−) cancer cell lines were assessed for physical, biochemical, and biological characteristics. Compared to the VHL(+) cells, VHL(−) cells produce significantly more exosomes that augment epithelial-to-mesenchymal transition (EMT) and migration of VHL(+) cells. Using a Cre- loxP exosome reporter system, the fluorescent color conversion and migration were correlated with dose-dependent delivery of VHL(−) exosomes. VHL(−) exosomes even induced a complete cascade of distant metastasis when added to VHL(+) tumor xenografts in a duck chorioallantoic membrane (dCAM) model, while VHL (+) exosomes did not. Therefore, this study supports that exosomes from VHL(−) cells could mediate critical cell-to-cell crosstalk to promote metastasis in RCC.
Keywords exosomes ; metastasis ; renal cell carcinoma ; EMT ; cell–cell communication ; CAM model ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code 610
Language English
Publishing date 2023-12-01T00:00:00Z
Publisher MDPI AG
Document type Article ; Online
Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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