title: DHA-mediated regulation of lung cancer cell migration is not directly associated with Gelsolin or Vimentin expression.
abstract: OBJECTIVE
  Deaths associated with cancer metastasis have steadily increased making the need for newer, anti-metastatic therapeutics imparative. Gelsolin and vimentin, actin binding proteins expressed in metastatic tumors, participate in actin remodelling and regulate cell migration. Docosahexaenoic acid (DHA) limits cancer cell proliferation and adhesion but the mechanisms involved in reducing metastatic phenotypes are unknown. We aimed to investigate the effects of DHA on gelsolin and vimentin expression, and ultimately cell migration and proliferation, in this context.
  
  
  METHODS
  Non-invasive lung epithelial cells (MLE12) and invasive lung cancer cells (A549) were treated with DHA (30μmol/ml) or/and 8 bromo-cyclic adenosine monophosphate (8 Br-cAMP) (300μmol/ml) for 6 or 24h either before (pre-treatment) or after (post-treatment) plating in transwells. Migration was assessed by the number of cells that progressed through the transwell. Gelsolin and vimentin expression were measured by Western blot and confocal microscopy in cells, and by immunohistochemistry in human lung cancer biopsy samples.
  
  
  RESULTS
  A significant decrease in cell migration was detected for A549 cells treated with DHA verses control but this same decrease was not seen in MLE12 cells. DHA and 8 Br-cAMP altered gelsolin and vimentin expression but no clear pattern of change was observed. Immunofluorescence staining indicated slightly higher vimentin expression in human lung tissue that was malignant compared to control.
  
  
  CONCLUSIONS
  Collectively, our data indicate that DHA inhibits cancer cell migration and further suggests that vimentin and gelsolin may play secondary roles in cancer cell migration and proliferation, but are not the primary regulators.
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. Electronic address: mehboob.ali@nationwidechildrens.org.
authors.forename: Mehboob
authors.initials: M
authors.lastname: Ali
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Heyob
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
authors.forename: Lynette K
authors.initials: LK
authors.lastname: Rogers
mesh_terms: D000072283:A549 Cells; D002465:Cell Movement / Q000187:drug effects*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D018260:Gelsolin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000378:metabolism*
chemical_list: D018260:Gelsolin; D014746:Vimentin; D004281:Docosahexaenoic Acids
keywords: Actin binding proteins; Docosahexaenoic acid; Lung cancer; Metastasis and actin dynamics; Migration