Abstract 4396: Caveolin-1 as an oncopromoter in solidtumors: A role mediated by STAT3 <i>in vitro</i>.
Authors: Anna Gasperi-Campani, Fabia Pancotti, Laura Roncuzzi
Journal: Cancer Research (2013)

Abstract Introduction Caveolin-1(Cav-1) is a multifunctional scaffolding protein essential structural constituent of caveolae, regulating multiple processes in cancer. A growing body of evidence links elevated expression of Cav-1 to an aggressive phenotype of cancer cells and to a poor prognosis in several tumors. The molecular mechanisms underlying the pro-survival and tumor-promoting functions of Cav-1 and the down-stream mediators of Cav-1 functional role in metastatic cancer have jet to be fully identified. The aim of the present work was to prosecute the investigation on such molecular pathways in solid tumors, based on our recent data obtained in cell lines from SCLC (SCLC-R1) and NSCLC (RAL) and from glioblastoma (A-172) where we demonstrated an oncopromoter activity of Cav-1 through the activation of STAT3 signaling pathway. Here we present the data obtained in a cell line from osteosarcoma (143B), where Cav-1 was highly expressed. Methods Cav-1 was knocked-down by siRNA using the transfection reagent oligofectamine. Cell proliferation was assessed by Trypan Blue exclusion test and by MTT test. Protein expressions were evaluated by Western Blotting. Results The siRNA-mediated down-regulation of Cav-1 caused the arrest of proliferation in the cell line, which remains stable up to 24 h after the removal of siRNA and then gradually returns to normal levels. Interestingly, both Cav-1 expression and proliferation goes down and turn up in the same way and at the same extent. A marked reduction of cyclin D1 and of CDK4 expression was evident in the cells transfected with Cav-1 siRNA and consequently of phosphoRb. The down-stream effector was STAT3 in the 143B osteosarcoma cell line, due to a significant induction of SOCS-1. Conclusions Together, our findings obtained in malignant tumors like SCLC, NSCLC, glioblastoma and osteosarcoma indicate that Cav-1 silencing induces an arrest of proliferation in vitro in each of them by inhibiting the pathway mediated by STAT3, through different upstream molecules depending on tumor: AKT and ERK in metastatic lung cancer, c-Src and p38 alpha in glioblastoma and SOCS-1 in osteosarcoma. These results confirm that Cav-1 exerts a role as a promoter of cancer proliferation and its activity strictly depends on cell/tumor type. They indicate the necessity to study this protein's function in each specific tumor context and provide new insights into the molecular mechanisms underlying the pro-survival and tumor-promoting functions of Cav-1. Grants from MIUR (RFO,PRIN), Roberto Pallotti's Legacy and Cornelia Pallotti's Legacy for Cancer Research, University of Bologna, Italy Citation Format: Anna Gasperi-Campani, Fabia Pancotti, Laura Roncuzzi. Caveolin-1 as an oncopromoter in solidtumors: A role mediated by STAT3 in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4396. doi:10.1158/1538-7445.AM2013-4396