title: Lung cancer cell invasion and expression of intercellular adhesion molecule-1 (ICAM-1) are attenuated by secretory phospholipase A₂ inhibition.
abstract: OBJECTIVE
  Invasive lung tumors are associated with intercellular adhesion molecule-1 (ICAM-1) expression. Secretory phospholipase A(2) (sPLA(2)) enzymes produce inflammatory mediators that stimulate ICAM-1 expression, and upregulation of PLA(2) activity can enhance metastasis. We hypothesize a link between sPLA(2) activity, ICAM-1 expression, and tumor cell invasion. We propose that inhibition of sPLA(2) modulates ICAM-1 expression in cancer cells and attenuates their invasiveness.
  
  
  METHODS
  Human lung adenocarcinoma cells (A549) were treated with an ICAM-1 blocking antibody and assayed for invasion. Lung cancer cells (A549 and H358) were then treated with an sPLA(2) inhibitor and evaluated by immunoblotting for ICAM-1 expression. Next cells (A549) treated with sPLA(2) inhibitor were assayed for invasion. Finally, sPLA(2) messenger RNA and protein expression were evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunofluorescence microscopy, respectively. Statistical analysis was performed by the Student t test or analysis of variance, as appropriate.
  
  
  RESULTS
  Antibody blockade of ICAM-1 decreased lung cancer cell invasion. sPLA(2) inhibition significantly reduced ICAM-1 expression and invasion. sPLA(2) inhibition also significantly decreased sPLA(2) mRNA expression and immunofluorescent staining of sPLA(2).
  
  
  CONCLUSIONS
  sPLA(2) plays a significant role in mediating the inflammatory signals that induce ICAM-1 expression in lung cancer cells. Inhibition of the enzyme can significantly decrease ICAM-1 expression and subsequent cancer cell invasion. This lays the groundwork for further investigation into the cellular mechanisms of sPLA(2) and its role in lung cancer.
authors.affiliation: Section of General Thoracic Surgery, Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Yu
authors.forename: Miral R
authors.initials: MR
authors.lastname: Sadaria
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Meng
authors.forename: Sanchayita
authors.initials: S
authors.lastname: Mitra
authors.forename: Lihua
authors.initials: L
authors.lastname: Ao
authors.forename: David A
authors.initials: DA
authors.lastname: Fullerton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weyant
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D000704:Analysis of Variance; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D054497:Phospholipases A2, Secretory