IGF-1 and its receptor in esophageal cancer: association with adenocarcinoma and visceral obesity

Suzanne L Doyle, Claire L Donohoe, Stephen P Finn, Julia M Howard, Fiona E Lithander, John V Reynolds, Graham P Pidgeon, Joanne Lysaght

Research output: Contribution to journalArticle (Academic Journal)peer-review

71 Citations (Scopus)

Abstract

OBJECTIVES: 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).

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)196-204
Number of pages9
JournalAmerican Journal of Gastroenterology
Volume107
Issue number2
DOIs
Publication statusPublished - Feb 2012

Keywords

  • Adenocarcinoma
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell
  • Cell Proliferation
  • Esophageal Neoplasms
  • Esophagus
  • Female
  • Humans
  • Insulin-Like Growth Factor I
  • Male
  • Middle Aged
  • Obesity
  • Receptor, IGF Type 1
  • Journal Article

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