Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma

作者：Taylor Chase; Loomans Holli A; Le Bras Gregoire F; Koumangoye Rainelli B; Romero Morales Alejandra I; Quast Laura L; Zaika Alexander I; El Rifai Wael; Andl Thomas; Andl Claudia D^*

来源：Oncotarget, 2015, 6(33): 34228-34244.

DOI：10.18632/oncotarget.5349

• Barrett's esophagus
• esophageal adenocarcinoma
• SOX9

TGF beta 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.

• 出版日期2015-10-27