title: Interleukin-6: a villain in the drama of pancreatic cancer development and progression.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a poor prognosis and little treatment options. The development and progression of the disease is fostered by inflammatory cells and cytokines. One of these cytokines is interleukin-6 (IL-6), which plays an important role in a wide range of biologic activities.
  
  
  METHODS
  A systematic search of PubMed was performed to identify relevant studies using key words such as interleukin-6, inflammatory cytokines, inflammation and pancreatic cancer or PDAC. Articles related to IL-6 and pancreatic cancer were systematically reviewed.
  
  
  RESULTS
  IL-6 is elevated in the serum of pancreatic cancer patients and correlates with cachexia, advanced tumor stage and poor survival. Its expression is enhanced by hypoxia and proteins involved in pancreatic cancer development like Kras, mesothelin or ZIP4. IL-6 in turn contributes to the generation of a pro-tumorigenic microenvironment and is probably involved in angiogenesis and metastasis. In experimental mouse models of PDAC, IL-6 was important for the development and progression of precursor lesions.
  
  
  CONCLUSIONS
  IL-6 emerges as a key player in pancreatic cancer development and progression, and hence should be considered as a new therapeutic target.
authors.affiliation: Division of Molecular Oncology, Institute for Experimental Cancer Research, CCC-North, University of Kiel, D-24105 Kiel, Germany. hkalthoff@email.uni-kiel.de.
authors.forename: Reinhild
authors.initials: R
authors.lastname: Holmer
authors.forename: Freya A
authors.initials: FA
authors.lastname: Goumas
authors.forename: Georg H
authors.initials: GH
authors.lastname: Waetzig
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D015195:Drug Design; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D000090204:Mesothelin; D058990:Molecular Targeted Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment; D000093242:Interleukin-6 Inhibitors
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018836:Inflammation Mediators; D015850:Interleukin-6; D000090204:Mesothelin; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C000715528:Msln protein, mouse