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

• Published in: International journal of molecular sciences Vol. 24; no. 24; p. 17307
• Main 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.12.2023
• Subjects: Angiogenesis; CAM model; Carcinoma, Renal Cell - pathology; Cells; cell–cell communication; Communication; EMT; exosomes; Exosomes - metabolism; Humans; Hypoxia; Kidney cancer; Kidney Neoplasms - metabolism; Metastasis; Morphology; renal cell carcinoma; Tumors; Von Hippel-Lindau Tumor Suppressor Protein - genetics; Von Hippel-Lindau Tumor Suppressor Protein - metabolism; cell–cell communication; renal cell carcinoma; CAM model; metastasis; EMT; exosomes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242417307

Exosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the 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- 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 (+) exosomes did not. Therefore, this study supports that exosomes from VHL(-) cells could mediate critical cell-to-cell crosstalk to promote metastasis in RCC.