Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma.

Taylor C, Loomans HA, Le Bras GF, Koumangoye RB, Romero-Morales AI, Quast LL, Zaika AI, El-Rifai W, Andl T, Andl CD
Oncotarget. 2015 6 (33): 34228-44

PMID: 26447543 · PMCID: PMC4741448 · DOI:10.18632/oncotarget.5349

TGFβ signaling has been implicated in the metaplasia from squamous epithelia to Barrett's esophagus and, ultimately, esophageal adenocarcinoma. The role of the family member Activin A in Barrett's tumorigenesis is less well established. As tumorigenesis is influenced by factors in the tumor microenvironment, such as fibroblasts and the extracellular matrix, we aimed to determine if epithelial cell-derived Activin affects initiation and progression differently than Activin signaling stimulation from a mimicked stromal source. Using Barrett's esophagus cells, CPB, and the esophageal adenocarcinoma cell lines OE33 and FLO-1, we showed that Activin reduces colony formation only in CPB cells. Epithelial cell overexpression of Activin increased cell migration and invasion in Boyden chamber assays in CPB and FLO-1 cells, which exhibited mesenchymal features such as the expression of the CD44 standard form, vimentin, and MT1-MMP. When grown in organotypic reconstructs, OE33 cells expressed E-cadherin and Keratin 8. As mesenchymal characteristics have been associated with the acquisition of stem cell-like features, we analyzed the expression and localization of SOX9, showing nuclear localization of SOX9 in esophageal CPB and FLO-1 cells.In conclusion, we show a role for autocrine Activin signaling in the regulation of colony formation, cell migration and invasion in Barrett's tumorigenesis.

MeSH Terms (12)

Activins Adenocarcinoma Barrett Esophagus Blotting, Western Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic Enzyme-Linked Immunosorbent Assay Esophageal Neoplasms Fluorescent Antibody Technique Humans Neoplasm Invasiveness

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