Response gene to complement 32 expression in macrophages augments paracrine stimulation-mediated colon cancer progression

Abstract

M2-polarized tumor associated macrophages (TAMs) play an important role in tumor progression. It has been reported that response gene to complement 32 (RGC-32) promotes M2 macrophage polarization. However, whether RGC-32 expression in macrophages could play a potential role in tumor progression remain unclear. Here we identified that increasing RGC-32 expression in colon cancer and tumor associated macrophages was positively correlated with cancer progression. In vitro studies confirmed that colon cancer cells upregulated RGC-32 expression of macrophages via secreting TGF-β1. RGC-32 expression promoted macrophage migration. In addition, stimulation of HCT-116 cells with the condition mediums of RGC-32-silienced or over-expressed macrophages affected tumor cell colony formation and migration via altered COX-2 expression. In an animal model, macrophages with RGC-32 knockdown significantly decreased the expression of COX-2 and Ki67 in the xenografts, and partly inhibited tumor growth. Together, our results provide the evidences for a critical role of TGF-β1/RGC-32 pathway in TAMs and colon cancer cells during tumor progression.

Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis

“…In the TME, TAMs and tumor cells promote tumor cell proliferation through the secretion of cytokines. In vitro studies confirmed that colon cancer cells upregulated the expression of RGC-32 in macrophages by secreting TGF-β1, and RGC-32 promoted the migration of macrophages and further accelerated the proliferation of colon cancer cells [61]. Yu, X. et al reported that overexpression of C-X-C-motif receptor 4 (CXCR4) in the intestinal epithelial mucosa can promote epithelial-mesenchymal transition (EMT) and macrophage infiltration in colonic tissue, leading to colitis-associated tumorigenesis and progression [62].…”

Role of RGC-32 in multiple sclerosis and neuroinflammation – few answers and many questions

“…Microglia are CNS-resident cells with an instrumental role in driving neuroinflammation ( 71 ). Evidence suggests that RGC-32 regulates macrophage differentiation and functions in various pathologies ( 72 – 74 ), and since macrophages share the same developmental origin as microglia ( 75 ), we assume that RGC-32 also plays an important role in these cells. In fact, RGC-32 has been shown to be expressed by cells with a microglial morphology in MS brains ( 27 ).…”

Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors

“…TAMs are prevalent in the TME of patients with CRC [ 31 ]. TAMs in the TME are predominantly the M2-type, which are important in cancer cell proliferation and metastasis [ 61 ]. A low M1/M2 ratio indicates poor prognosis and facilitates tumor cell metastasis [ 31 , 62 , 63 ].…”