RRC ID 74588
Author Tanigawa K, Tsukamoto S, Koma YI, Kitamura Y, Urakami S, Shimizu M, Fujikawa M, Kodama T, Nishio M, Shigeoka M, Kakeji Y, Yokozaki H.
Title S100A8/A9 Induced by Interaction with Macrophages in Esophageal Squamous Cell Carcinoma Promotes the Migration and Invasion of Cancer Cells via Akt and p38 MAPK Pathways.
Journal Am J Pathol
Abstract Tumor-associated macrophages are associated with more malignant phenotypes of esophageal squamous cell carcinoma (ESCC) cells. Previously, an indirect co-culture assay of ESCC cells and macrophages was used to identify several factors associated with ESCC progression. Herein, a direct co-culture assay of ESCC cells and macrophages was established, which more closely simulated the actual cancer microenvironment. Direct co-cultured ESCC cells had significantly increased migration and invasion abilities, and phosphorylation levels of Akt and p38 mitogen-activated protein kinase (MAPK) compared with monocultured ESCC cells. According to a cDNA microarray analysis between monocultured and co-cultured ESCC cells, both the expression and release of S100 calcium binding protein A8 and A9 (S100A8 and S100A9), which commonly exist and function as a heterodimer (herein, S100A8/A9), were significantly enhanced in co-cultured ESCC cells. The addition of recombinant human S100A8/A9 protein induced migration and invasion of ESCC cells via Akt and p38 MAPK signaling. Both S100A8 and S100A9 silencing suppressed migration, invasion, and phosphorylation of Akt and p38 MAPK in co-cultured ESCC cells. Moreover, ESCC patients with high S100A8/A9 expression exhibited significantly shorter disease-free survival (P = 0.005) and cause-specific survival (P = 0.038). These results suggest that S100A8/A9 expression and release in ESCC cells are enhanced by direct co-culture with macrophages and that S100A8/A9 promotes ESCC progression via Akt and p38 MAPK signaling pathways.
Volume 192(3)
Pages 536-552
Published 2022-3-1
DOI 10.1016/j.ajpath.2021.12.002
PII S0002-9440(21)00531-9
PMID 34954212
MeSH Calgranulin A* / genetics Calgranulin B* / genetics Calgranulin B* / metabolism Esophageal Neoplasms* / pathology Esophageal Squamous Cell Carcinoma* / pathology Humans Macrophages / metabolism Mitogen-Activated Protein Kinase 14* / metabolism Proto-Oncogene Proteins c-akt / metabolism Tumor Microenvironment p38 Mitogen-Activated Protein Kinases / metabolism
IF 3.491
Human and Animal Cells TE-9(RCB1988) TE-10(RCB2099) TE-11(RCB2100)