The insulin-like growth factor (IGF) pathway and visceral obesity have been independently linked with esophageal cancer. This study aimed to delineate the differential and interlinked role of visceral obesity and the IGF-1 system in esophageal adenocarcinoma and esophageal squamous-cell carcinoma (SCC).
IGF-1 receptor (IGF-1R) mRNA and protein were examined in esophageal SCC (KYSE 410, OE21) and esophageal adenocarcinoma (OE19, OE33) cell lines by western blotting. Tumor cell proliferation in response to IGF-1 was assessed by bromodeoxyuridine incorporation assay. In esophageal tumor sections, expression of IGF-1R and CD68+ cell numbers were assessed by immunohistochemistry. IGF-1 was measured in serum from esophageal cancer patients, Barrett's esophagus patients, and healthy controls by enzyme-linked immunosorbent assay.
Higher IGF-1R protein expressions were observed in SCC cells compared with esophageal adenocarcinoma cells however only adenocarcinoma cell lines significantly increased proliferation in response to IGF-1 (P<0.01). Serum IGF-1 levels were highest in esophageal adenocarcinoma patients (P<0.01) and higher in viscerally obese vs. nonobese (P<0.05) patients. In resected esophageal cancer, increased expression of IGF-1R was observed in the tumor and invasive edge compared with tumor-associated stroma (P<0.05), which coincided with increased CD68+ cells in stromal tissue surrounding invasive tumor edge (P<0.01).
This novel study examined the differential role of the IGF system in esophageal adenocarcinoma and SCC, and its association with visceral obesity. These results indicate that the IGF-1 axis has a key role in malignant progression of esophageal cancer, and represents a plausible mechanism through which visceral obesity impacts on esophageal adenocarcinoma risk and tumor biology.
1 Department of Surgery, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital and University of Dublin, Trinity College, Dublin, Ireland
2 Department of Histopathology, Central Pathology Laboratories, St James's Hospital and University of Dublin, Trinity College, Dublin, Ireland
3 Department of Diagnostic Imaging, St James's Hospital, Dublin, Ireland
4 Department of Clinical Medicine, University of Dublin, Trinity College, Dublin, Ireland
Correspondence: John V. Reynolds, MA, MB, MCh, FRCSI, Department of Surgery, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital and University of Dublin, Trinity College, Dublin 8, Ireland. E-mail: firstname.lastname@example.org
Received 16 February 2011; accepted 10 September 2011
published online 6 December 2011