title: Effect of perineoplasm perinephric adipose tissues on migration of clear cell renal cell carcinoma cells: a potential role of WNT signaling.
abstract: To investigate the cellular and molecular interactions between clear-cell renal cell carcinoma (ccRCC) and perinephric adipose tissue (PAT), perineoplasm PAT, PAT away from the neoplasm, renal sinus and subcutaneous adipose tissues were collected at the time of renal surgery for renal masses and conditioned medium (CM) was generated from 62 patients. Perineoplasm PAT CMs from 44 out of 62 (about 71%) of patients with ccRCC or benign renal diseases (e.g. oncocytomas, angiomyolipomas, multicystic kidney, interstitial fibrosis, etc.) enhanced the migration of CaKi-2 cells. Perineoplasm PAT CMs from ccRCC significantly increased migration of ACHN and CaKi-2 cells by ~8.2 and ~2.4 folds, respectively, relative to those from benign renal diseases, whereas there is no significant difference in migration between ccRCC and benign renal diseases in CMs collected from culturing PAT away from neoplasm, renal sinus and subcutaneous adipose tissues. High Fuhrman Grade was associated with increased migration of Caki-2 cells by perineoplasm PAT CMs. Perineoplasm PATs from pT3 RCCs overexpressed multiple WNTs and their CMs exhibited higher WNT/ß-catenin activity and increased the migration of Caki-2 cells compared to CMs from benign neoplasms. Addition of secreted WNT inhibitory factor-1 recombinant protein into perineoplasm PAT CMs completely blocked the cell migration. These results indicate that WNT related factors from perineoplasm PAT may promote progression of local ccRCC to locally advanced (pT3) disease by increasing ccRCC cell mobility.
authors.affiliation: Department of Urology, University of California, Irvine, CA 92868, USA.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zi
authors.affiliation: Department of Urology, University of California, Irvine, CA 92868, USA.
authors.forename: Achim
authors.initials: A
authors.lastname: Lusch
authors.affiliation: Department of Urology, University of California, Irvine, CA 92868, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Blair
authors.affiliation: Department of Urology, University of California, Irvine, CA 92868, USA.
authors.forename: Zhamshid
authors.initials: Z
authors.lastname: Okhunov
authors.affiliation: Department of Urology, University of California, Irvine, CA 92868, USA.
authors.forename: Noriko N
authors.initials: NN
authors.lastname: Yokoyama
authors.affiliation: Department of Urology, University of California, Irvine, CA 92868, USA.
authors.forename: Shuman
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Urology, University of California, Irvine, CA 92868, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Baker
authors.affiliation: Department of Urology, University of California, Irvine, CA 92868, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Huynh
authors.affiliation: Department of Urology, University of California, Irvine, CA 92868, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: Landman
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D051176:beta Catenin
keywords: WNT; fat; migration; proliferation; renal cell carcinoma