title: Cancer-associated fibroblasts promote renal cell carcinoma progression.
abstract: The aim of this study was to determine the effect of cancer-associated fibroblasts (CAFs) on renal cell carcinoma (RCC) tumor proliferation, migration, and development of drug resistance, thus underlying their potential as therapeutic targets in RCC patients. CAFs were grown in primary cultures. The in vitro model of interaction of RCC cell lines with CAFs was established. The influence of CAFs on the proliferation and migration ability as well as sensitivity to everolimus of RCC cells was further analyzed. Furthermore, Western blotting analysis was performed to examine the mechanisms mediating the effect of CAFs on RCC cells. The results of the MTT assay showed that coculture with CAFs increased the proliferation activity of both 786-O and Caki-1 cells compared with serum-free medium controls. The migration ability of RCC cell lines was also significantly enhanced after coculture treatment compared with untreated control. The inhibition effect of everolimus on 786-O and Caki-1 cells abrogated in cocultures with CAFs. The sensitivity of both two cell lines to everolimus was dramatically decreased when cocultured with CAFs. RCC cells cocultured with CAFs resulted in the activation of both proliferation-related (Erks) and survival-related (Akt) pathways. These data indicate that CAFs have an important role in supporting and promoting RCC. The interaction of CAFs with RCC cell lines stimulates tumor cell proliferation and migration and induces resistance to everolimus in RCC cells, suggesting that target of the tumor microenvironment may be a novel targeted therapies for RCC.
authors.affiliation: Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, 200 Pujian Road, Shanghai, 200127, China.
authors.forename: Yunze
authors.initials: Y
authors.lastname: Xu
authors.forename: Yongning
authors.initials: Y
authors.lastname: Lu
authors.forename: Jiajia
authors.initials: J
authors.lastname: Song
authors.forename: Baijun
authors.initials: B
authors.lastname: Dong
authors.forename: Wen
authors.initials: W
authors.lastname: Kong
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Yiran
authors.initials: Y
authors.lastname: Huang
mesh_terms: D002292:Carcinoma, Renal Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D000068338:Everolimus; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000068338:Everolimus; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020123:Sirolimus