Role of tumor derived versican in experimental malignant pleural mesothelioma

Abstract

Introduction Versican, an extracellular matrix protein, is overexpressed in several solid tumors and it promotes tumor progression through cell and non cell autonomous mechanisms. However its function in mesothelioma has not been investigated. Hypothesis Tumor cell versican promotes mesothelioma progression and corresponding malignant pleural effusion (MPE) accumulation. Methods Versican expressing ΑE17 and ΑΒ1 mesothelioma cells stably transfected with short hairpin versican plasmids or control ΑE17 and ΑΒ1 cells were injected into the pleural cavity of syngeneic C57BL/6 and Balb/c mice respectively to create pleural mesotheliomas. Fourteen days later the animals were sacrificed and the tumor mass and MPE were collected and quantified. Intratumoral and pleural immune subsets were assessed using flow cytometry. Results Versican silencing caused a significant reduction in mesothelioma mass (mean difference=0.299±0.05 g, p in C57BL/6 and 0.436±0.06 g, p in Balb/c mice), as well as in MPE volume (mean dif.= 395.1±137.9 μl, p in C57BL/6 and 370.2±41.49 μl, p in Balb/c mice) [fig.1]. Mice harboring versican deficient tumors presented fewer intratumoral and intrapleural macrophages and neutrophils, but only fewer MPE Tregs, compared to the control animals. Conclusion Tumor cell versican promotes mesothelioma progression and MPE accumulation through promoting tumor cell survival and shaping a tumor friendly inflammatory millieu .