MIF promotes perineural invasion through EMT in salivary adenoid cystic carcinoma

Abstract

Macrophage migration inhibitory factor (MIF) is a prominent orchestrator during the onset and progression of cancer. Recently, MIF was detected in salivary adenoid cystic carcinoma (SACC). However, its functional effect in perineural invasion (PNI) of SACC remained unknown. To illuminate the effect of MIF in genesis of PNI in SACC, we examined the expression of MIF, epithelial‐to‐mesenchymal transition (EMT)‐related markers, and Schwann cell markers by immunohistochemical analysis in 158 cases of SACC samples. Meanwhile, the correlation between MIF and PNI of SACC species was analyzed. Our data indicated that MIF expression was associated with PNI of SACC significantly. In vitro, the silence and overexpression experiments of MIF were performed in SACC cell lines. The ability of migration, invasion and PNI could be inhibited significantly by siRNA‐mediated MIF silence, and the occurrence of EMT and Schwann‐like cell differentiation was also inhibited by MIF silence in SACC‐LM cells. Overexpression of MIF in SACC‐83 cells using expressive plasmid showed the opposite effects. Our findings identified that an association between PNI and MIF expression existed. MIF may promote PNI of SACC by participating in cytoskeletal reorganization and pseudo foot formation induced by EMT and the Schwann‐like cell differentiation of SACC cells.

A Novel Immune-Associated Gene Signature for Overall Survival Prediction in Patients with Oral Squamous Cell Carcinoma

“…For example, Yang et al found that MIF can drive the malignant progression of pancreatic cancer [ 16 ]. Zhang et al found that MIF can promote the perineural infiltration of salivary adenoid cystic carcinoma [ 17 ]. Wang et al found that AREG can regulate the epithelial-mesenchymal transition of pancreatic carcinoma cells [ 18 ].…”

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Where We Are and Where We Need to Go

“…Furthermore, the BDNF/TRKB axis is also reported to have a role in the epithelial-mesenchymal transition (EMT) process in SACC. And the study by Mei Zhang et al proposed a correlation between PNI and MIF expression that MIF may promote the PNI of SACC by participating in cytoskeletal reorganization and pseudopod formation induced by Schwann-like cell differentiation of EMT and SACC cells ( 59 ). Despite the limited number of studies concerning the association between EMT and PNI, EMT is likely to play an invasive critical role in PNI progression, given the enhanced migration and abilities of cancer cells after EMT ( 42 ).…”

Extracellular Vesicles from Carcinoma-Associated Fibroblasts Promote Epithelial-Mesenchymal Transition of Salivary Adenoid Cystic Carcinoma via Interleukin-6

“…Hoffmann et al and his colleagues reported that IL-6 serum levels increased in some SACC patients, compared with healthy controls [40]. Besides IL-6, other cytokines may contribute to SACC invasion and metastasis, such as transforming growth factor-β1 [41], macrophage migration inhibitory factor [42], and tumor necrosis factor receptor-associated factor 6 [43], et al Further studies are necessary to elucidate the exact roles of cytokines on SACC invasion. IL-6 exerts its biological functions by binding to its receptor sIL-6R to activate JAK/STAT3 signaling pathway, which controls the occurrence and development of tumors [44][45][46].…”