title: Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop.
abstract: BACKGROUND
  Pancreatic cancer shows a highly aggressive and infiltrative growth pattern and is characterized by an abundant tumor stroma known to interact with the cancer cells, and to influence tumor growth and drug resistance. Cancer cells actively take part in the production of extracellular matrix proteins, which then become deposited into the tumor stroma. Type IV collagen, an important component of the basement membrane, is highly expressed by pancreatic cancer cells both in vivo and in vitro. In this study, the cellular effects of type IV collagen produced by the cancer cells were characterized.
  
  
  METHODS
  The expression of type IV collagen and its integrin receptors were examined in vivo in human pancreatic cancer tissue. The cellular effects of type IV collagen were studied in pancreatic cancer cell lines by reducing type IV collagen expression through RNA interference and by functional receptor blocking of integrins and their binding-sites on the type IV collagen molecule.
  
  
  RESULTS
  We show that type IV collagen is expressed close to the cancer cells in vivo, forming basement membrane like structures on the cancer cell surface that colocalize with the integrin receptors. Furthermore, the interaction between type IV collagen produced by the cancer cell, and integrins on the surface of the cancer cells, are important for continuous cancer cell growth, maintenance of a migratory phenotype, and for avoiding apoptosis.
  
  
  CONCLUSIONS
  We show that type IV collagen provides essential cell survival signals to the pancreatic cancer cells through an autocrine loop.
authors.affiliation: Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Öhlund
authors.forename: Oskar
authors.initials: O
authors.lastname: Franklin
authors.forename: Erik
authors.initials: E
authors.lastname: Lundberg
authors.forename: Christina
authors.initials: C
authors.lastname: Lundin
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
mesh_terms: D017209:Apoptosis / Q000235:genetics; D019898:Autocrine Communication / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D016023:Integrins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D016023:Integrins