title: CD9P-1 expression correlates with the metastatic status of lung cancer, and a truncated form of CD9P-1, GS-168AT2, inhibits in vivo tumour growth.
abstract: BACKGROUND
  Loss of CD9 expression has been correlated with a higher motility and metastatic potential of tumour cells originating from different organs. However, the mechanism underlying this loss is not yet understood.
  
  
  METHODS
  We produced a truncated form of partner 1 of CD9 (CD9P-1), GS-168AT2, and developed a new monoclonal antibody directed towards the latter. We measured the expression of CD9 and CD9P-1 in human lung tumours (hLTs), and monitored the level of CD9 in NCI-H460, in vitro and in vivo, in the presence and absence of GS-168AT2.
  
  
  RESULTS
  Loss of CD9 is inversely related to the expression of CD9P-1, which correlates with the metastatic status of hLT (n=55). In vitro, GS-168AT2 is rapidly internalised and degraded at both the membrane and cytoplasm of NCI-H460, and this correlates with the association of GS-168AT2 with both CD9 and CD81. Intraperitoneal injections of GS-168AT2 in NCI-H460-xenografted Nude mice led to drastic inhibition of tumour growth, as well as to the downregulation of CD9, but not of CD81, in the tumour core.
  
  
  CONCLUSIONS
  These findings show for the first time that CD9P-1 expression positively correlates with the metastatic status of hLT, and that the upregulation of CD9P-1 expression could be one of the mechanisms underlying the loss of CD9 in solid tumours. Our study also reveals that, under certain conditions, loss of CD9 could be a tumour growth-limiting phenomenon rather than a tumour growth-promoting one.
authors.affiliation: Gene Signal Research Center, 4 Rue Pierre Fontaine, Evry 91000, France.
authors.forename: W
authors.initials: W
authors.lastname: Guilmain
authors.forename: S
authors.initials: S
authors.lastname: Colin
authors.forename: E
authors.initials: E
authors.lastname: Legrand
authors.forename: J P
authors.initials: JP
authors.lastname: Vannier
authors.forename: C
authors.initials: C
authors.lastname: Steverlynck
authors.forename: M
authors.initials: M
authors.lastname: Bongaerts
authors.forename: M
authors.initials: M
authors.lastname: Vasse
authors.forename: S
authors.initials: S
authors.lastname: Al-Mahmood
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D009363:Neoplasm Proteins; C486331:PTGFRN protein, human