TGF-β Inhibition Through Combinatory Strategies Suppresses Proliferation and Invasiveness in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor associated with asbestos exposure, which represents a current problem. MPM is characterized by a poor prognosis and an unsatisfactory therapeutic approach. Therefore, improving MPM prognosis is the real challenge for research today. Regarding preclinical data, Transforming Growth Factor-β (TGF-β) plays a crucial role in cancer, and its alteration has been associated with tumor progression and invasiveness, in particular through the Epithelial to Mesenchymal Transition (EMT) event. We investigated the role of TGF-β inhibition in proliferation, cell cycle, migration, and invasiveness in human MPM cells. Data obtained clearly highlighted how TGF-β inhibition, through the silencing or treatment of MPM cells with antibody anti-TGF-β (Fresolimumab), significantly reduces cell proliferation (MTT, PCNA) and prevents metastasis, reducing EMT and decreasing the invasiveness and migration of MPM cells. Finally, we also evaluated TGF-β inhibitory effects in 3D MPM cellular models (spheroids), highlighting a significant slowdown in the growth rate of spheroids treated with anti-TGF-β antibody or Fresolimumab, confirming the results previously obtained. Taken as a whole, targeting TGF-β will represent a starting point for future improvements in MPM management. This is particularly important as we foresee a growing increase in MPM in the coming years.