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