Protumoral effect of macrophage through Axl activation on mucoepidermoid carcinoma.
Chiu, Kuo-Chou 1,2; Lee, Chien-Hsing 3; Liu, Shyun-Yeu 4; Yeh, Chi-Tai 5; Huang, Ren-Yeong 2; Yuh, Da-Yo 2; Cheng, Jen-Chan 1,6; Chou, Yu-Ting 7; Shieh, Yi-Shing 2
[Article] Journal of Oral Pathology & Medicine. 43(7):538-544, August 2014.

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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.

(C) 2014 John Wiley & Sons, Ltd