Colony‑stimulating factor 1 receptor inhibition blocks macrophage infiltration and endometrial cancer cell proliferation

Abstract

Tumor-associated macrophages (TAMs) promote the progression of endometrial cancer (EC), but the mechanism of TAM in EC cell proliferation remains unclear. It was found that colony stimulating factor (CSF)-1 and CSF-1 receptor (CSF-1R) were highly expressed in EC tissues of patients and two EC cell lines (ECC-1 and HEC-1A). Using wound-healing and chemotactic migration assays to evaluate the role of EC cells in the induction of macrophage migration, it was found that the supernatant of EC cells promoted macrophage cell line (U937) migration; however, the migration capacity of U937 weakened when CSF-1R was blocked. Subsequently, inhibition of CSF-1 expression in EC cells also restrained U937 migration. Additionally, blocking CSF-1R by PLX3397 treatment in U937 cells inhibited EC cell proliferation in a co-culture system by inhibiting the expression of proliferation-associated proteins (Janus kinase-1, phosphoinositide 3-kinase, AKT, cyclin kinase 2, 4 and retinoblastoma-associated protein). Together, these results demonstrated that CSF-1 secreted by EC cells promoted macrophage migration; similarly, CSF-1-stimulated macrophages promoted EC cell proliferation. These results suggested that the interaction between CSF-1 and its receptor served an important role in promoting macrophage infiltration and progression of EC.

lncRNA-Xist/miR-101-3p/KLF6/C/EBPα axis promotes TAM polarization to regulate cancer cell proliferation and migration

“…Furthermore, many studies confirmed M2 macrophages could promote tumor cell proliferation and migration. 30 , 31 , 32 Therefore, to explore whether Xist could promote tumor proliferation and migration by regulating macrophage polarization, we cocultured human breast cancer cells (MCF-7) and human ovarian (OV) cancer cells with M1 conditional medium after transfection with sh-NC or sh-Xist-1 or sh-Xist-2 plasmids. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays showed that the cell viabilities of MCF-7 and OV cells in sh-Xist-1 and sh-Xist-2 groups were increased compared to the sh-NC group ( Figure 3 C).…”

Pathological angiogenesis and inflammation in tissues

“…TAMs that originate from circulating monocytes are recruited to the hypoxic tumor area by tumor-derived factors, such as colony-stimulating factor-1 (CSF-1), VEGF-A, and chemokine (C-C motif) ligand 2 (CCL2) (Lin et al 2019;Pathria et al 2019). CSF-1 is a chemotactic factor for most populations of macrophages that induces proliferation, chemotaxis, and differentiation of monocytes (Hua et al 2019;Pathria et al 2019). The binding of CCL2 and its receptor, chemokine (C-C motif) receptor 2 (CCR2), mediates the migration and infiltration of monocytes/macrophages to primary or metastatic tumors (Yoshimura 2018;Liu et al 2020).…”

Colony Stimulating Factor-1 and its Receptor in Gastrointestinal Malignant Tumors

“…CSF-1 secreted by endometrial cancer cells promotes the migration and proliferation of macrophages. The results show that the interaction between CSF-1 and its receptor plays an important role in promoting macrophage infiltration and endometrial cancer progression 48 .…”