title: Epidermal growth factor mediates detachment from and invasion through collagen I and Matrigel in Capan-1 pancreatic cancer cells.
abstract: BACKGROUND
  Pancreatic adenocarcinoma is a highly invasive neoplasm. Epidermal growth factor (EGF) and its receptor are over expressed in pancreatic cancer, and expression correlates with invasion and metastasis. We hypothesized that EGF receptor and integrin signalling pathways interact in mediating cellular adhesion and invasion in pancreatic cancer, and that invasiveness correlates temporally with detachment from extracellular matrix.
  
  
  METHODS
  We tested this hypothesis by investigating the role of EGF in mediating adhesion to and invasion through collagen I and Matrigel in the metastatic pancreatic adenocarcinoma cell line Capan-1. Adhesion and invasion were measured using in vitro assays of fluorescently-labeled cells. Adhesion and invasion assays were also performed in the primary pancreatic adenocarcinoma cell line MIA PaCa-2.
  
  
  RESULTS
  EGF inhibited adhesion to collagen I and Matrigel in Capan-1 cells. The loss of adhesion was reversed by AG825, an inhibitor of erbB2 receptor signalling and by wortmannin, a PI3K inhibitor, but not by the protein synthesis inhibitor cycloheximide. EGF stimulated invasion through collagen I and Matrigel at concentrations and time courses similar to those mediating detachment from these extracellular matrix components. Adhesion to collagen I was different in MIA PaCa-2 cells, with no significant change elicited following EGF treatment, whereas treatment with the EGF family member heregulin-alpha elicited a marked increase in adhesion. Invasion through Matrigel in response to EGF, however, was similar to that observed in Capan-1 cells.
  
  
  CONCLUSIONS
  An inverse relationship exists between adhesion and invasion capabilities in Capan-1 cells but not in MIA PaCa-2 cells. EGF receptor signalling involving the erbB2 and PI3K pathways plays a role in mediating these events in Capan-1 cells.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, and The Puget Sound Veterans Administration Health Care System, Seattle, Washington, USA. ashirk@u.washington.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Shirk
authors.forename: Rahul
authors.initials: R
authors.lastname: Kuver
mesh_terms: D001672:Biocompatible Materials; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D003094:Collagen; D024042:Collagen Type I; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011509:Proteoglycans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D003094:Collagen; D024042:Collagen Type I; D004338:Drug Combinations; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D039421:Integrin alpha2; D019012:Integrin beta1; D007797:Laminin; D019869:Phosphatidylinositol 3-Kinases; D011509:Proteoglycans; D018719:Erb-b2 Receptor Tyrosine Kinases; C059485:matrigel