title: Leukemia inhibitory factor increases the invasiveness of trophoblastic cells through integrated increase in the expression of adhesion molecules and pappalysin 1 with a concomitant decrease in the expression of tissue inhibitor of matrix metalloproteinases.
abstract: OBJECTIVE
  To identify the invasion-associated molecules during leukemia inhibitory factor-(LIF-)mediated increase in the invasion of trophoblast cells.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Research institution.
  
  
  METHODS
  None.
  
  
  METHODS
  Cultured trophoblastic HTR-8/SVneo cells were treated with LIF.
  
  
  METHODS
  Matrigel matrix-based invasion assay of HTR-8/SVneo cells. Signaling molecules associated with LIF-mediated increase in invasion were investigated by Western blot, cDNA microarray, quantitative reverse transcriptase polymerase chain reaction, immunofluorescence, immunohistochemistry, and gene silencing by siRNA.
  
  
  RESULTS
  Treatment of HTR-8/SVneo cells with LIF (50 ng/mL) led to a significant increase in invasion. Treatment with LIF also led to an increase in nuclear localization of activated STAT1 and STAT3. Among 237 differentially expressed genes after LIF treatment, expression of pappalysin 1, SERPINB3, podoplanin, integrin β3, ID1, ICAM1, and so on went up, while tissue inhibitor of matrix metalloproteinase 1 (TIMP1), TIMP2, and TIMP3 went down significantly. The presence of several of these proteins has also been demonstrated in human trophoblast cells. Silencing of pappalysin 1 led to a significant reduction in basal as well as LIF-mediated invasiveness of HTR-8/SVneo cells.
  
  
  CONCLUSIONS
  Identification of novel molecules associated with a LIF-mediated increase in trophoblastic cell invasion may facilitate our understanding of implantation biology.
authors.affiliation: Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Suman
authors.forename: Nachiket
authors.initials: N
authors.lastname: Shembekar
authors.forename: Satish Kumar
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000378:metabolism* / Q000494:pharmacology; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D014328:Trophoblastic Neoplasms / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D053605:Leukemia Inhibitory Factor; D019714:Tissue Inhibitor of Metalloproteinases; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human