An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer

Abstract

Growing evidence shows that granulocyte macrophage colony-stimulating factor (GM-CSF) has progression-promoting potentials in certain solid tumors, which is largely attributed to the immunomodulatory function of this cytokine in tumor niches. However, little is known about the effect of GM-CSF on cancer cells. Herein, we show that chronic exposure of colon cancer cells to GM-CSF, which harbor its receptor, leads to occurrence of epithelial to mesenchymal transition (EMT), in time and dose-dependent manners. These GM-CSF-educated cancer cells exhibit enhanced ability of motility in vitro and in vivo. Furthermore, GM-CSF stimulation renders colon cancer cells more resistant to cytotoxic agents. Mechanistic investigation reveals that MAPK/ERK signaling and EMT-inducing transcription factor ZEB1 are critical to mediate these effects of GM-CSF. In specimen of CRC patients, high-level expression of GM-CSF positively correlates with local metastases in lymph nodes. Moreover, the co-expression of GM-CSF and its receptors as well as phosphorylated ERK1/2 are observed. Thus, our study for the first time identifies a progression-promoting function of GM-CSF in colon cancer by inducing EMT.

Characterization of a p53/miR-34a/CSF1R/STAT3 Feedback Loop in Colorectal Cancer

“…Interestingly, CSF2/GM-CSF has recently been shown to induce EMT in colon cancer cells and may thereby contribute to CRC progression as well. 51 …”

A Novel Endogenous Damage Signal, CSF-2, Activates Multiple Beneficial Functions of Adipose Tissue-Derived Mesenchymal Stem Cells

“…These results indicate that CD116 may act as a functional receptor to mediate the various beneficial effects of CSF-2 on stem cells. Because CD116 is known to be involved in regulating diverse biological functions, including apoptosis, 46 cell growth, 47 and multi-lineage differentiation, 48 the role of CSF-2 in activating CD116 implies its potential role in the regulation of stem cell migratory and differentiation capabilities.…”

Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia

“…High expression of IL‐8 and VEGF is associated with induction of angiogenesis and progression of prostate cancer, ovarian cancer, and melanoma, and thus, these factors have been recently proposed as novel players in inflammation and tumour fibrosis . In addition, Chen et al . described that the GM‐CSF acts directly in epithelial–mesenchymal transitions (EMT) by inducing MAPK activation in a murine colon cancer cell line.…”