Interleukin-22 is frequently expressed in small- and large-cell lung cancer and promotes growth in chemotherapy-resistant cancer cells

J Thorac Oncol. 2013 Aug;8(8):1032-42. doi: 10.1097/JTO.0b013e31829923c8.

Abstract

Introduction: In lung cancer, interleukin-22 (IL-22) expression within primary tissue has been demonstrated, but the frequency and the functional consequence of IL-22 signaling have not been addressed. This study aims at analyzing the cellular effects of IL-22 on lung carcinoma cell lines and the prognostic impact of IL-22 tissue expression in lung cancer patients.

Methods: Biological effects of IL-22 signaling were investigated in seven lung cancer cell lines by Western blot, flow cytometry, real-time polymerase chain reaction, and proliferation assays. Tumor tissue specimens of two cohorts with a total of 2300 lung cancer patients were tested for IL-22 expression by immunohistochemistry. IL-22 serum concentrations were analyzed in 103 additional patients by enzyme-linked immunosorbent assay.

Results: We found the IL-22 receptor 1 (IL-22-R1) to be expressed in six of seven lung cancer cell lines. However IL-22 signaling was functional in only four cell lines, where IL-22 induced signal transducer activator of transcription 3 phosphorylation and increased cell proliferation. Furthermore, IL-22 induced the expression of antiapoptotic B-cell lymphoma 2, but did not rescue tumor cells from carboplatin-induced apoptosis. Cisplatin-resistant cell lines showed a significant up-regulation of IL-22-R1 along with a stronger proliferative response to IL-22 stimulation. IL-22 was preferentially expressed in small- and large-cell lung carcinoma (58% and 46% of cases, respectively). However, no correlation between IL-22 expression by immunohistochemistry and prognosis was observed.

Conclusion: IL-22 is frequently expressed in lung cancer tissue. Enhanced IL-22-R1 expression and signaling in chemotherapy-refractory cell lines are indicative of a protumorigenic function of IL-22 and may contribute to a more aggressive phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Large Cell / chemistry*
  • Carcinoma, Large Cell / drug therapy
  • Carcinoma, Large Cell / pathology
  • Cell Line, Tumor
  • Child
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukins / analysis
  • Interleukins / physiology*
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Interleukin / analysis
  • Small Cell Lung Carcinoma / chemistry
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / pathology*

Substances

  • Interleukins
  • Receptors, Interleukin
  • interleukin-22 receptor
  • interleukin-22