• IL-32 isoforms work, in some cases, as a growth factor for mesothelioma. • IL-32 isoforms regulate IL-17A-enhanced VEGF-A and CXCL8 secretion from mesothelioma. • Overexpressed IL-32β regulates mesothelioma growth and VEGF-A and CXCL8 production. • Overexpressed IL-32β enhances growth and VEGF-A and CXCL8 secretion via PI3K pathway. • Overexpressed IL-32β potentiates angiogenesis and in vivo growth of mesothelioma. In this study, we sought to elucidate the roles of the interleukin (IL)-32β and IL-32γ in mesothelioma cell growth, and vascular endothelial growth factor (VEGF)-A and C-X-C motif chemokine ligand 8 (CXCL8) expression. IL-32 elicited a growth-promoting effect against one of the six mesotheliomas lines and exerted diverse regulatory functions in VEGF-A and CXCL8 secretion from mesotheliomas stimulated with or without IL-17A. Retroviral-mediated transduction of mesothelioma lines with IL-32γ resulted in enhanced IL-32β expression, which facilitated or suppressed the in vitro growth, and VEGF-A and CXCL8 expression. Overexpressed IL-32β-augmented growth and VEGF-A and CXCL8 production were mainly mediated through the phosphatidylinositol-3 kinase (PI3K) signaling pathway. On the other hand, overexpressed IL-32β-deceased growth was mediated through mitogen-activated protein kinase (MAPK) pathway. NCI-H2373IL-32γ tumors grew faster than NCI-H2373Neo tumors in a xenograft model, which was associated with increased vascularity. These findings indicate that IL-32 are involved in the regulation of growth and angiogenic factor production in mesotheliomas. [ABSTRACT FROM AUTHOR]