Interleukin-32 beta stimulates migration of MDA-MB-231 and MCF-7cells via the VEGF-STAT3 signaling pathway

Abstract

Background IL-32 is known to play an important role in inflammatory and autoimmune disease responses. In addition to its role in these responses, IL-32 and its different isoforms have in recent years been implicated in the development of various cancers. As of yet, the role of IL-32 in breast cancer has remained largely unknown. Results By performing immunohistochemical assays on primary breast cancer samples, we found that the level of IL-32 beta expression was positively correlated with tumor size, number of lymph node metastases and tumor stage. In addition, we found that breast cancer-derived MDA-MB-231 cells exogenously expressing IL-32 beta exhibited increased migration and invasion capacities. These increased capacities were found to be associated with an increased expression of the epithelial mesenchymal transition (EMT) markers vimentin and Slug, the latter of which is responsible for the increase in vimentin transcription. To next investigate whether IL-32 beta enhances migration and invasion through a soluble factor, we determined the levels of several migration-stimulating ligands, and found that the production of VEGF was increased by IL-32 beta. In addition, we found that IL-32 beta-induced VEGF increased migration and invasion through STAT3 activation. Conclusion The IL-32 beta-VEGF-STAT3 pathway represents an additional pathway that mediates the migration and invasion of breast cancer cells under the conditions of normoxia and hypoxia.