Increased Expression and Secretion of Interleukin-6 in Patients with Barrett's Esophagus

Katerina Dvorakova, Claire M. Payne, Lois Ramsey, Hana Holubec, Richard Sampliner, Jessica Dominguez, Bohuslav Dvorak, Harris Bernstein, Carol Bernstein, Anil Prasad, Ronnie Fass, Haiyan Cui, Harinder Garewal

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81 Scopus citations

Abstract

Purpose: Barrett's esophagus (BE) is a common premalignant lesion of the distal part of the esophagus that arises as a consequence of chronic duodenogastroesophageal reflux. Interleukin (IL)-6 is a pleiotropic cytokine that regulates immune defense mechanisms and hematopoiesis. In addition, IL-6 may also be involved in malignant transformation and tumor progression. IL-6 has been shown to inhibit apoptosis. The major aim of this study was to evaluate expression of IL-6 in BE at the protein and mRNA levels. In addition, we tested whether proteins that are associated with IL-6 signaling, phosphorylated signal transducer and activator of transcription 3 and two antiapoptotic proteins, Bcl-xL and Mcl-1, are also expressed in the same tissues. Experimental Design: Biopsies of duodenum, BE, and squamous epithelium were evaluated by using a human cytokine protein array, ELISA, real-time PCR, and immunohistochemistry. Results: Increased IL-6 levels were found to be secreted from BE tissue compared with duodenum or squamous epithelium from sites adjacent or 5 cm away from the BE lesion. IL-6 mRNA was also elevated in BE compared with duodenum or squamous epithelium in five of seven patients. Immunohistochemical studies confirmed IL-6 expression in intestinal glandular epithelium in BE tissue. Activated signal transducer and activator of transcription 3, Mcl-1, and Bcl-xL are present at higher levels in BE glands, with lower levels being found in duodenum or squamous epithelium Conclusions: These data, taken together, suggest that elevated IL-6 levels in BE may contribute to the development of apoptosis resistance, thereby placing this epithelium at higher risk of developing malignancy.

Original languageEnglish (US)
Pages (from-to)2020-2028
Number of pages9
JournalClinical Cancer Research
Volume10
Issue number6
DOIs
StatePublished - Mar 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Dvorakova, K., Payne, C. M., Ramsey, L., Holubec, H., Sampliner, R., Dominguez, J., Dvorak, B., Bernstein, H., Bernstein, C., Prasad, A., Fass, R., Cui, H., & Garewal, H. (2004). Increased Expression and Secretion of Interleukin-6 in Patients with Barrett's Esophagus. Clinical Cancer Research, 10(6), 2020-2028. https://doi.org/10.1158/1078-0432.CCR-0437-03