Table 1.

The role cancer-associated fibroblasts play in esophageal cancer

Stages during esophageal cancer development	Functional factors expressed by CAFs	In RE/BE/ESCC/EAC	Positive/negative function	Mechanism or postulated mechanisma	References
Premalignant condition	IL-6	RE	+	Promoting inflammation	[22]
	HB-EGF	BE	+	Promoting metaplasia	[5]
	COX2	BE	+	Promoting proliferation through PGE	[25]
Carcinogenesis	TGFβ1 and HGF	ESCC	+	Unknown	[27]
	TβRII	ESCC	−	TGF-β signaling pathway	[28]
	TLR-4	EAC	+	COX-2/MAPK pathwaya	[29]
Proliferation and angiogenesis	FGF	ESCC	+	FGF/FGFR pathways	[6]
	HGF	ESCC	+	HGF/MET pathways	[6]
	FGFR2	ESCC	+	Creating suitable environment for cancer cells proliferation	[2]
	Wnt2	ESCC	+	Wnt/β-catenin signaling pathway	[34]
	VEGF	ESCC	+	Promoting angiogenesis	[14]
	VEGF	EAC	+	Promoting angiogenesis	[36]
Invasion and metastasis	HGF	ESCC	+	HGF/MET signaling pathway	[10]
	TGFβI	ESCC	+	Promoting migration and invasion	[8]
	Wnt2	ESCC	+	Promoting EMT of cancer cells	[34]
	Periostin	EAC	+	PI3k–Akt pathway	[9]

Through secreting factors, CAFs exerted an influence on esophageal cancer development

RE reflux esophagitis, BE Barrett’s esophagus, IL interleukin, HB-EGF heparin-binding EGF-like factor, (COX)-2 cyclooxygenase, TGFβ1 transforming growth factor β1, HGF hepatocyte growth factor, TβRII TGFβ receptor 2, TLR-4 toll-like receptor-4, FGF fibroblast growth factors, FGFR fibroblast growth factors receptor, Wnt2 wingless-type MMTV integration site family member 2, VEGF vascular endothelial growth factor, TGFβI transforming growth factor beta-induced protein, CA IX carbonic anhydrase IX, PGE prostaglandin E, MAPK mitogen-activated protein kinases, EMT epithelial-mesenchymal transition

^a postulated mechanism