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- Title
Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma.
- Authors
Flora, Kailey; Ishihara, Moe; Zhang, Zhicheng; Bowen, Elizabeth S.; Wu, Aimee; Ayoub, Tala; Huang, Julian; Cano-Ruiz, Celine; Jackson, Maia; Reghu, Kaveeya; Ayoub, Yasmeen; Zhu, Yazhen; Tseng, Hsian-Rong; Zhou, Z. Hong; Hu, Junhui; Wu, Lily
- 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.
- Subjects
RENAL cell carcinoma; EXOSOMES; CANCER cells; EXTRACELLULAR vesicles; CHORIOALLANTOIS; TUMOR suppressor genes
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 24, p17307
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms242417307