title: Up-regulation of TGM2 with ITGB1 and SDC4 is important in the development and metastasis of renal cell carcinoma.
abstract: OBJECTIVE
  Tissue transglutaminase (TGM2) up-regulation is involved in the progression and dissemination of carcinomas through β1 integrin (ITGB1) association. Given that TGM2 interaction with syndecan-4 (SDC4) on the cell surface is important in the activation of ITGB1 and integrin-mediated survival signaling, we investigated the roles of TGM2, ITGB1, and SDC4 in the development and metastasis of renal cell carcinoma (RCC).
  
  
  METHODS
  Expression levels of TGM2, ITGB1, and SDC4 mRNA were analyzed in primary tumor samples (n = 95) and their healthy counterparts in addition to control and RCC epithelial cell lines. TGM2 catalytic activity in 60 randomly selected patient samples was measured by enzyme-linked sorbent plate assay.
  
  
  RESULTS
  TGM2 expression ratio showed a significant 2.9-fold decrease in 67 (70.5%) of the primary RCC tumors (P <0.0001) independent of clinical covariates, including tumor node metastasis (TNM) staging and histopathologic grading. For the remaining 28 (29.5%) tumors, a 1.95-fold increase was recorded in the TGM2 expression levels, which also showed a significant increase in ITGB1 and SDC4 expression levels in 82.6% of the overexpression cases (P <0.001). Up-regulation of TGM2 along with ITGB1 and SCD4 was associated with metastasis and a marked decrease in tumor necrosis. Consistently, RCC cell lines exhibited higher levels of TGM2 expression compared with the control epithelial cell line with a significant up-regulation of ITGB1 and SCD4 recorded for the metastatic lines.
  
  
  CONCLUSIONS
  Our findings suggest that TGM2 up-regulation along with ITGB1 and SDC4 plays an important role in the development of RCC tumors and advanced RCC with metastasis.
authors.affiliation: Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey.
authors.forename: Merve
authors.initials: M
authors.lastname: Erdem
authors.affiliation: Department of Urology, Istanbul University, Istanbul, Turkey.
authors.forename: Selcuk
authors.initials: S
authors.lastname: Erdem
authors.affiliation: Department of Urology, Istanbul University, Istanbul, Turkey.
authors.forename: Oner
authors.initials: O
authors.lastname: Sanli
authors.affiliation: Department of Systems Engineering, Yeditepe University, Istanbul, Turkey.
authors.forename: Halis
authors.initials: H
authors.lastname: Sak
authors.affiliation: Department of Pathology, Istanbul University, Istanbul, Turkey.
authors.forename: Isin
authors.initials: I
authors.lastname: Kilicaslan
authors.affiliation: Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey.
authors.forename: Fikrettin
authors.initials: F
authors.lastname: Sahin
authors.affiliation: Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey. Electronic address: dilek.telci@yeditepe.edu.tr.
authors.forename: Dilek
authors.initials: D
authors.lastname: Telci
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D053671:Syndecan-4 / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D019012:Integrin beta1; C508304:SDC4 protein, human; D053671:Syndecan-4; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Integrin β1; Metastasis; Renal cell carcinoma; Syndecan-4; Tissue transglutaminase