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- W3201634116 abstract "Abstract To study the impact of intratumoral VHL heterogeneity observed in patient ccRCC primary tumors, we engineered VHL gene deletion in three RCC models, including a new primary tumor cell line derived from an aggressive metastatic ccRCC. The VHL gene-deleted (VHL-KO) cells underwent epithelial-to-mesenchymal transition (EMT) and showed diminished proliferation and tumorigenicity compared to the parental, VHL-expressing (VHL+) cells. Renal tumors with either VHL+ or VHL-KO cells alone exhibit minimal metastatic potential. Interestingly, tumors with both cells displayed rampant lung metastasis, highlighting a novel cooperative metastatic mechanism. The poorly proliferative VHL-KO cells stimulated the proliferation, EMT and motility of neighboring VHL+ cells. We found that periostin (POSTN), a protein product overexpressed and secreted by VHL- cells, promoted metastasis by enhancing the motility of VHL-WT cells and facilitating vascular escape of tumor cells. Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models. Our work suggests a new strategy to halt progression in ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor." @default.
- W3201634116 created "2021-09-27" @default.
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- W3201634116 date "2021-09-10" @default.
- W3201634116 modified "2023-09-27" @default.
- W3201634116 title "Tumor Heterogeneity in VHL Drives Metastasis in Clear Cell Renal Cell Carcinoma" @default.
- W3201634116 doi "https://doi.org/10.21203/rs.3.rs-846239/v1" @default.
- W3201634116 hasPublicationYear "2021" @default.
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