Association between duodenal contents reflux and squamous cell carcinoma--establishment of an esophageal cancer cell line derived from the metastatic tumor in a rat reflux model.

Abstract

Squamous cell carcinoma (SCC) of the human esophagus has a multifactorial etiology involving several environmental and/or genetic factors. Recently, gastroesophageal reflux has been implicated as a causative factor in upper aerodigestive tract carcinogenesis. The development of esophageal squamous cell carcinoma (ESCC) in a duodenal contents reflux model without any known carcinogen present has been reported previously. In this study, the duodenal contents reflux model without gastrectomy was used. At 60 weeks post-operatively, all surviving animals had malignant lesions as follows: ESCC (40%), esophageal adenocarcinoma (EAC) (20%) and adenosquamous carcinoma (40%). In one subject, a well-differentiated ESCC was detected with thoracic dissemination and metastases in lymph nodes. A novel cell line, designated ESCC-DR, was established from the thoracic metastatic tumor at the 60th post-operative week. These cells were transplanted into nude mice, and the developed nodules represented a well differentiated ESCC, resembling that of the parent site. Duodenal contents reflux has a great potential for malignant initiation and plays a role in developing not only EAC but also ESCC.