Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma
Exosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the <i>von Hippel-Lindau (VHL)</i> tumor suppressor gene and those that do not is instrumental to distant metastasis in renal cell carcinoma...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/24/17307 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kailey Flora |
| collection | DOAJ |
| description | Exosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the <i>von Hippel-Lindau (VHL)</i> 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-<i>loxP</i> 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 <i>VHL</i>(+) exosomes did not. Therefore, this study supports that exosomes from VHL(−) cells could mediate critical cell-to-cell crosstalk to promote metastasis in RCC. |
| first_indexed | 2024-03-08T20:41:27Z |
| format | Article |
| id | doaj.art-0b8718b19b73402ca13d5daf155b711f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:41:27Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0b8718b19b73402ca13d5daf155b711f2023-12-22T14:13:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241730710.3390/ijms242417307Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell CarcinomaKailey Flora0Moe Ishihara1Zhicheng Zhang2Elizabeth S. Bowen3Aimee Wu4Tala Ayoub5Julian Huang6Celine Cano-Ruiz7Maia Jackson8Kaveeya Reghu9Yasmeen Ayoub10Yazhen Zhu11Hsian-Rong Tseng12Z. Hong Zhou13Junhui Hu14Lily Wu15Department of Bioengineering, University of California, Los Angeles, CA 90095, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USADepartment of Computational and Systems Biology, University of California, Los Angeles, CA 90095, USADepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USADepartment of Physiology, University of California, Los Angeles, CA 90095, USADepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USADepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USADepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USASchool of Medicine, Saint Louis University, St. Louis, MO 63104, USACalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USACalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USACalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USAExosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the <i>von Hippel-Lindau (VHL)</i> 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-<i>loxP</i> 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 <i>VHL</i>(+) exosomes did not. Therefore, this study supports that exosomes from VHL(−) cells could mediate critical cell-to-cell crosstalk to promote metastasis in RCC.https://www.mdpi.com/1422-0067/24/24/17307exosomesmetastasisrenal cell carcinomaEMTcell–cell communicationCAM model |
| spellingShingle | 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 Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma International Journal of Molecular Sciences exosomes metastasis renal cell carcinoma EMT cell–cell communication CAM model |
| title | Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma |
| title_full | Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma |
| title_fullStr | Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma |
| title_full_unstemmed | Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma |
| title_short | Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma |
| title_sort | exosomes from von hippel lindau null cancer cells promote metastasis in renal cell carcinoma |
| topic | exosomes metastasis renal cell carcinoma EMT cell–cell communication CAM model |
| url | https://www.mdpi.com/1422-0067/24/24/17307 |
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