title: Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells.
abstract: BACKGROUND
  Invasion is an important early step in the metastatic cascade and is the primary cause of death of prostate cancer patients. In order to invade, cells must detach from the primary tumor. Cell-cell and cell-ECM interactions are important regulators of cohesion--a property previously demonstrated to mediate cell detachment and invasion. The studies reported here propose a novel role for α5β1 integrin--the principle mediator of fibronectin matrix assembly (FNMA)--as an invasion suppressor of prostate cancer cells.
  
  
  METHODS
  Using a combination of biophysical and cell biological methods, and well-characterized prostate cancer cell lines of varying invasiveness, we explore the relationship between cohesion, invasiveness, and FNMA.
  
  
  RESULTS
  We show that cohesion is inversely proportional to invasive capacity. We also show that more invasive cells express lower levels of α5β1 integrin and lack the capacity for FNMA. Cells were generated to over-express either wild-type α5 integrin or an integrin in which the cytoplasmic domain of α5 was replaced with that of α2. The α2 construct does not promote FNMA. We show that only wild-type α5 integrin promotes aggregate compaction, increases cohesion, and reduces invasion of the more aggressive cells, and that these effects can be blocked by the 70-kDa fibronectin fragment.
  
  
  CONCLUSIONS
  We propose that restoring capacity for FNMA in deficient cells can increase tumor intercellular cohesion to a point that significantly reduces cell detachment and subsequent invasion. In prostate cancer, this could be of therapeutic benefit by blocking an early key step in the metastatic cascade.
authors.affiliation: Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, CAB 7319, New Brunswick, NJ 08901, USA.
authors.forename: Dongxuan
authors.initials: D
authors.lastname: Jia
authors.forename: Ildiko
authors.initials: I
authors.lastname: Entersz
authors.forename: Christine
authors.initials: C
authors.lastname: Butler
authors.forename: Ramsey A
authors.initials: RA
authors.lastname: Foty
mesh_terms: D000704:Analysis of Variance; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D013500:Surface Tension
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1