Protumoral effect of macrophage through Axl activation on mucoepidermoid carcinoma

Abstract

Objective: This study aims to test the potential involvement of Axl signaling in the protumoral effect of tumor-associated macrophages (TAMs) in mucoepidermoid carcinoma (MEC). Materials and Methods: We carried out co-cultured experiments by incubation of MEC cells (UT-MUC-1) and macrophages (THP-1) and examined Axl activation status. The expression of MMPs and behavior change were examined in UT-MUC-1 cells. The effect of Axl signaling on co-cultured cancer cells was further investigated by knockdown Axl expression and suppression by Axl-specific inhibitor R428. Results: Activation of Axl signaling and increased expression and activity of MMP-2 and MMP-9 along with increased invasion/migration ability in MEC cells were observed when co-cultured with TAMs. Upon knockdown of Axl in MEC or addition of R428 in the co-cultured system, these co-cultured effects were diminished. Conclusion: TAMs play a protumoral role in MEC via activation of the Axl signaling pathway, up-regulating MMPs expression, and increasing invasion/migration ability. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.