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, Giuseppe Lucarelli

International Journal of Molecular Sciences(2023)

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摘要
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.
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关键词
exosomes,metastasis,renal cell carcinoma,EMT,cell-cell communication,CAM model
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