title: Alterations in integrin expression modulates invasion of pancreatic cancer cells.
abstract: BACKGROUND
  Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood.
  
  
  METHODS
  In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression.
  
  
  RESULTS
  Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion.
  
  
  CONCLUSIONS
  Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. naomi.walsh@dcu.ie
authors.forename: Naomi
authors.initials: N
authors.lastname: Walsh
authors.forename: Martin
authors.initials: M
authors.lastname: Clynes
authors.forename: John
authors.initials: J
authors.lastname: Crown
authors.forename: Norma
authors.initials: N
authors.lastname: O'Donovan
mesh_terms: D023102:Anoikis / Q000235:genetics; D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: D016023:Integrins; D034741:RNA, Small Interfering