ANXA10 induction by interaction with tumor‐associated macrophages promotes the growth of esophageal squamous cell carcinoma

Abstract

Tumor‐associated macrophages (TAMs) have important roles in the growth, angiogenesis and progression of various tumors. Although we have demonstrated the association of an increased number of infiltrating CD204+ TAMs with poor prognosis in esophageal squamous cell carcinomas (ESCCs), the roles of TAMs in ESCC remain unclear. Here, to study the effects of TAMs on the tumor microenvironment of ESCCs, we established a co‐culture assay using a human ESCC cell line and TAM‐like peripheral blood monocyte‐derived macrophages and performed a cDNA microarray analysis between monocultured and co‐cultured ESCC cell lines. Our qRT‐PCR confirmed that in the co‐cultured ESCC cell lines, CYP1A1, DHRS3, ANXA10, KLK6 and CYP1B1 mRNA were highly up‐regulated; AMTN and IGFL1 mRNA were down‐regulated. We observed that the high expression of a calcium‐dependent phospholipid‐binding protein ANXA10 was closely associated with the depth of invasion and high numbers of infiltrating CD68+ and CD204+ TAMs and poor disease‐free survival (P = 0.0216). We also found ANXA10 promoted the cell growth of ESCC cell lines via the phosphorylation of Akt and Erk1/2 pathways in vitro. These results suggest that ANXA10 induced by the interaction with TAMs in the tumor microenvironment is associated with cell growth and poor prognosis in human ESCC tissues.

Annexin A10 Expression Is Associated With Poor Prognosis in Small Bowel Adenocarcinoma

“…Another limitation of this study is that the specific role of ANXA10 in SBA was not examined. The function of ANXA10 has been reported in several organs (13,14,20,21). In CRCs, ANXA10 expression has been correlated with microsatellite instability (21) and involves BRAF mutation and CpG island methylation (20).…”

“…Several carcinomas have been reported to express ANXA10, including carcinomas of the liver (12), gastrointestine (11), and oesophagus (13). We have previously reported that ANXA10 is associated with the gastric phenotype of gastric cancer through the regulation of pancreatic duodenal homeobox-1 (PDX1) (14) and that ANXA10 is associated with early-stage gastric cancer (15).…”

Loss of Annexin A10 Expression Is Associated with Poor Prognosis in Early Gastric Cancer

“…Immunohistochemical staining was performed according to several previous methods with some modifications including a western blotting study [ 5 , 8 ]. Paraffin-embedded tissue blocks were available for immunohistochemical evaluation in 103 representative slides.…”

<p>Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche</p>

“…105 CD204 + TAM can also increase the expression of tumor suppressor protein annexin A10 (ANXA10) in cancer cells, and promote the proliferation of ESCC cells through phosphorylation of Akt and Erk1/2 pathways. 106 The high expression of ANXA10 in cancer cells has been found to promote cancer cell growth and proliferation in a variety of tumors including lung cancer, 107 ovarian cancer, 108 and prostate cancer. 109 Indeed, various secreted factors such as Cyr61, 105 GDF15, 100,101,110 TGF-βRII, 100,111,112 and ANXA10 106 have been reported to be associated with poor prognosis of ESCC.…”

“…106 The high expression of ANXA10 in cancer cells has been found to promote cancer cell growth and proliferation in a variety of tumors including lung cancer, 107 ovarian cancer, 108 and prostate cancer. 109 Indeed, various secreted factors such as Cyr61, 105 GDF15, 100,101,110 TGF-βRII, 100,111,112 and ANXA10 106 have been reported to be associated with poor prognosis of ESCC. This series of studies revealed that TAMs could promote ESCC progression through strong secretory functions, and demonstrated the huge potential of TAMs-related pathways and molecules as novel therapeutic targets and biomarkers.…”