Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma

Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma. Flora, K., Ishihara, M., Zhang, Z., Bowen, E. S., Wu, A., Ayoub, T., Huang, J., Cano-Ruiz, C., Jackson, M., Reghu, K., Ayoub, Y., Zhu, Y., Tseng, H., Zhou, Z. H., Hu, J., & Wu, L. International Journal of Molecular Sciences, 24(24):17307, Multidisciplinary Digital Publishing Institute, January, 2023.
doi abstract bibtex

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.

@article{floraExosomesHippelLindauNullCancer2023,
  title = {Exosomes from {{Von Hippel-Lindau-Null Cancer Cells Promote Metastasis}} in {{Renal Cell Carcinoma}}},
  author = {Flora, Kailey and Ishihara, Moe and Zhang, Zhicheng and Bowen, Elizabeth S. and Wu, Aimee and Ayoub, Tala and Huang, Julian and {Cano-Ruiz}, Celine and Jackson, Maia and Reghu, Kaveeya and Ayoub, Yasmeen and Zhu, Yazhen and Tseng, Hsian-Rong and Zhou, Z. Hong and Hu, Junhui and Wu, Lily},
  year = {2023},
  month = jan,
  journal = {International Journal of Molecular Sciences},
  volume = {24},
  number = {24},
  pages = {17307},
  publisher = {Multidisciplinary Digital Publishing Institute},
  issn = {1422-0067},
  doi = {10.3390/ijms242417307},
  urldate = {2024-06-13},
  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.},
  copyright = {http://creativecommons.org/licenses/by/3.0/},
  langid = {english},
  keywords = {CAM model,cell-cell communication,EMT,exosomes,metastasis,renal cell carcinoma},
  file = {C:\Users\shervinnia\Zotero\storage\MN6LV7YD\Flora et al. - 2023 - Exosomes from Von Hippel-Lindau-Null Cancer Cells .pdf}
}

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