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Novel metastatic models of esophageal adenocarcinoma derived from FLO-1 cells highlight the importance of E-cadherin in cancer metastasis

Authors :
Liu, DS
Hoefnagel, SJM
Fisher, OM
Krishnadath, KK
Montgomery, KG
Busuttil, RA
Colebatch, AJ
Read, M
Duong, CP
Phillips, WA
Clemons, NJ
Liu, DS
Hoefnagel, SJM
Fisher, OM
Krishnadath, KK
Montgomery, KG
Busuttil, RA
Colebatch, AJ
Read, M
Duong, CP
Phillips, WA
Clemons, NJ
Publication Year :
2016

Abstract

There is currently a paucity of preclinical models available to study the metastatic process in esophageal cancer. Here we report FLO-1, and its isogenic derivative FLO-1LM, as two spontaneously metastatic cell line models of human esophageal adenocarcinoma. We show that FLO-1 has undergone epithelial-mesenchymal transition and metastasizes following subcutaneous injection in mice. FLO-1LM, derived from a FLO-1 liver metastasis, has markedly enhanced proliferative, clonogenic, anti-apoptotic, invasive, immune-tolerant and metastatic potential. Genome-wide RNAseq profiling revealed a significant enrichment of metastasis-related pathways in FLO-1LM cells. Moreover, CDH1, which encodes the adhesion molecule E-cadherin, was the most significantly downregulated gene in FLO-1LM compared to FLO-1. Consistent with this, repression of E-cadherin expression in FLO-1 cells resulted in increased metastatic activity. Importantly, reduced E-cadherin expression is commonly reported in esophageal adenocarcinoma and independently predicts poor patient survival. Collectively, these findings highlight the biological importance of E-cadherin activity in the pathogenesis of metastatic esophageal adenocarcinoma and validate the utility of FLO-1 parental and FLO-1LM cells as preclinical models of metastasis in this disease.

Details

Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1315704897
Document Type :
Electronic Resource