Abstract
Lung cancer is the leading cause of cancer death in the United States and around the world. Recent studies indicate that cancer-associated fibroblasts (CAFs) are involved in tumor growth, invasion and metastasis, however, the underling mechanisms remain unclear. In the present study, we investigated the role of interaction of interleukin 32 (IL-32) with integrin on the metastatic potential of lung cancer cells and related CAF pathway. We found that IL-32, an ‘RGD’ motif–containing cytokine, was found to be abundantly expressed in CAFs. Integrin β3 turned out to be up-regulated in non-small lung cancer (NSCLC) during epithelial–mesenchymal transition (EMT). CAF-derived IL-32 specifically bound to integrin β3 through the RGD motif, thus activating intracellular downstream p38 MAPK signalling in NSCLC cells. This signalling increased the expression of EMT markers and promoted tumor cell invasion. While, inhibition of IL-32 led to specific inactivation of p38 MAPK signalling in tumor cells. Furthermore, blockage of the p38 MAPK pathway also diminished IL-32-induced expression of EMT markers and NSCLC cell invasion and metastasis.
Keywords: NSCLC; MAPK; CAF; RGD
Copyright © 2020 by The American Society for BioMedicine and BM-Publisher, Inc.
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Research Article
DOI: http://dx.doi.org/10.18081/2333-5106/018-10/685-697
American Journal of BioMedicine Volume 8, Issue 3, pages 191-202
Received April 22, 2020; Accepted August 25, 2020; Published September 04, 2020