Calcium oxalate crystals trigger epithelial-mesenchymal transition and carcinogenic features in renal cells: a crossroad between kidney stone disease and renal cancer
Issued Date
2022-12-01
Resource Type
eISSN
21623619
Scopus ID
2-s2.0-85138694977
Journal Title
Experimental Hematology and Oncology
Volume
11
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Experimental Hematology and Oncology Vol.11 No.1 (2022)
Suggested Citation
Peerapen P., Boonmark W., Putpeerawit P., Thongboonkerd V. Calcium oxalate crystals trigger epithelial-mesenchymal transition and carcinogenic features in renal cells: a crossroad between kidney stone disease and renal cancer. Experimental Hematology and Oncology Vol.11 No.1 (2022). doi:10.1186/s40164-022-00320-y Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83526
Title
Calcium oxalate crystals trigger epithelial-mesenchymal transition and carcinogenic features in renal cells: a crossroad between kidney stone disease and renal cancer
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
Increasing evidence of association between kidney stone disease (KSD) and renal cell carcinoma (RCC) has been reported. Nevertheless, mechanism underlying such association remained unknown. Herein, we investigated the effects of calcium oxalate monohydrate (COM), a major crystalline component causing KSD, on induction of carcinogenic features in non-cancerous renal cells. COM crystals induced morphological changes from epithelial to fibroblast-like spindle shape. Additionally, COM increased spindle index and mesenchymal markers (fibronectin and vimentin) but declined epithelial markers (E-cadherin and zonula occludens-1). Moreover, COM down-regulated ARID1A, a tumor suppressor gene recently reported to be reversely associated with RCC, at both mRNA and protein levels. COM also down-regulated other RCC-related tumor suppressor genes, PTEN and VHL, but up-regulated oncogene TPX2. Finally, COM enhanced invading capability, cell-aggregate formation, chemoresistance to cisplatin, and secretion of an angiogenic factor (VEGF). These data indicate that COM crystals trigger epithelial-mesenchymal transition (EMT) and several carcinogenic features in the non-cancerous renal cells. These mechanisms may explain and strengthen the association between KSD and RCC.