title: IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling.
abstract: BACKGROUND
  Interleukin-22 (IL-22) has been recently highlighted owing to its biological significance in the modulation of tissue responses during inflammation. However, the role of IL-22 in carcinogenesis has remained unclear. Here, we investigated the pathophysiological significance of IL-22 expression in gastric cancer tissues and examined the mechanism by which IL-22 promotes gastric cancer cell invasion.
  
  
  METHODS
  Human gastric cancer specimens were analysed by immunohistochemistry for expression of IL-22 and IL-22 receptor 1 (IL-22R1). The effects of IL-22-induced STAT3 and ERK signalling on invasive ability of gastric cancer cells were examined using a small-interfering RNA system and specific inhibitors. AGS cells were co-cultured with cancer-associated fibroblasts (CAFs) from human gastric cancer tissues and assessed by invasion assay.
  
  
  RESULTS
  Interleukin-22 and its receptor were expressed in α-smooth muscle actin-positive stromal cells and tumour cells at the invasive front of gastric cancer tissues, respectively. The expression of IL-22 and IL-22R1 was significantly related to lymphatic invasion. Interleukin-22 treatment promoted the invasive ability of gastric cancer cells through STAT3 and ERK activation. The invasive ability of gastric cancer cells was significantly enhanced by co-culture with IL-22-expressing CAFs.
  
  
  CONCLUSIONS
  Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.affiliation: 1] Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan [2] Department of Geriatric Digestive Internal Medicine, Sichuan Academy of Medical Science & Sichuan People's Hospital, Chengdu 610072, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1] Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan [2] Department of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: C
authors.initials: C
authors.lastname: Sun
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kikuchi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Watari
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi 321-0293, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Imura
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi 321-0293, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fujimori
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sasako
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Miwa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D018123:Receptors, Interleukin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C494086:STAT3 protein, human; C415369:interleukin-22 receptor