title: Interleukin-22 is frequently expressed in small- and large-cell lung cancer and promotes growth in chemotherapy-resistant cancer cells.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine IV, Division of Clinical Pharmacology and Center of Integrated Protein Science, Ludwig-Maximilians Universität München, Member of the German Center for Lung Research, Munich, Germany. Sebastian.kobold@med.uni-muenchen.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kobold
authors.forename: Stefanie
authors.initials: S
authors.lastname: Völk
authors.forename: Till
authors.initials: T
authors.lastname: Clauditz
authors.forename: Natascha Jennifer
authors.initials: NJ
authors.lastname: Küpper
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Amanda
authors.initials: A
authors.lastname: Tufman
authors.forename: Peter
authors.initials: P
authors.lastname: Düwell
authors.forename: Michael
authors.initials: M
authors.lastname: Lindner
authors.forename: Ina
authors.initials: I
authors.lastname: Koch
authors.forename: Simon
authors.initials: S
authors.lastname: Heidegger
authors.forename: Simon
authors.initials: S
authors.lastname: Rothenfuer
authors.forename: Max
authors.initials: M
authors.lastname: Schnurr
authors.forename: Rudolf Maria
authors.initials: RM
authors.lastname: Huber
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002648:Child; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000032:analysis / Q000502:physiology*; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018123:Receptors, Interleukin / Q000032:analysis; D055752:Small Cell Lung Carcinoma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor