Merve Erdem1, Selcuk Erdem2, Oner Sanli2, Halis Sak3, Isin Kilicaslan4, Fikrettin Sahin1, Dilek Telci5. 1. Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey. 2. Department of Urology, Istanbul University, Istanbul, Turkey. 3. Department of Systems Engineering, Yeditepe University, Istanbul, Turkey. 4. Department of Pathology, Istanbul University, Istanbul, Turkey. 5. Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey. Electronic address: dilek.telci@yeditepe.edu.tr.
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). MATERIAL AND 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.
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). MATERIAL AND 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: Bruna Ribeiro Carneiro; Paulo Castanho A Pernambuco Filho; Ana Paula de Sousa Mesquita; Douglas Santos da Silva; Maria Aparecida S Pinhal; Helena B Nader; Carla Cristina Lopes Journal: PLoS One Date: 2014-12-30 Impact factor: 3.240
Authors: Mariana A Soares; Felipe C O B Teixeira; Miguel Fontes; Ana Lúcia Arêas; Marcelo G Leal; Mauro S G Pavão; Mariana P Stelling Journal: Biomed Res Int Date: 2015-10-19 Impact factor: 3.411