BACKGROUND _ AIMS: @entity5 cells with high metastatic potential and stem cell-like characteristics express the cell surface marker @entity1759 . @entity1759 isoforms that include the v6 exon are co-receptors for the receptor @entity4149 kinases MET and  @entity319 . We studied CD44v6 signaling in several @entity788 cell lines, and its role in @entity5 growth and @entity3 in several models of @entity788 . METHODS: We analyzed the effects of v6 peptides that interfere with the  co-receptor functions of CD44v6 for MET and @entity319 in  @entity5 and @entity3 grown from cells that express different @entity1759  isoforms, including CD44v6. The peptides were injected into @entity35 with @entity5 and @entity19 with orthotopic or xenograft @entity5 . We also tested the effects of the peptides in @entity19 with xenograft @entity5 grown from @entity1 @entity5 samples and @entity19 that express an oncogenic form of RAS and develop spontaneous @entity788 ( @entity24197  @entity19 ). We measured levels of CD44v6 messenger RNA (mRNA) in @entity788 tissues from 136 @entity1 . RESULTS: Xenograft @entity5 grown from @entity1 @entity5 cells  injected with v6 peptides were smaller and formed fewer @entity3 in @entity19 . The v6 peptide was more efficient than the MET inhibitor @entity9816 and/or the @entity319 inhibitor @entity6219 in reducing xenograft @entity5 growth and @entity3 . Injection of @entity24197 @entity19 with the v6 peptide increased their survival time. Injection of @entity19 and @entity35 bearing @entity3 with the v6 peptide induced regression of @entity3 . Higher levels of CD44v6 mRNA in @entity1 @entity788 tissues were associated with increased expression of MET, @entity5 @entity3 , and shorter @entity1 survival times. CONCLUSIONS: Peptide inhibitors of CD44v6 isoforms block @entity5 growth and @entity3 in several independent models of @entity788 . The v6 peptides induced regression of @entity3 . Levels of CD44v6 mRNA are  increased, along with those of MET mRNA, in @entity1 with metastatic @entity788 , compared with nonmetastatic @entity5 ; the increased levels correlated with shorter @entity1 survival time.

Inhibition of Tumor Growth and XXXX in @entity788 Models by Interference With CD44v6 Signaling.

@entity1 :: ('9606', 'Species') :: ['human', 'patient', 'patients'] @entity788 :: ('MESH:D010190', 'Disease') :: ['pancreatic tumor', 'pancreatic cancer', 'pancreatic tumors'] @entity6219 :: ('MESH:C516667', 'Chemical') :: ['pazopanib'] @entity5 :: ('MESH:D009369', 'Disease') :: ['syngeneic tumors', 'tumor', 'cancer', 'Cancer', 'tumors'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity9816 :: ('MESH:C551994', 'Chemical') :: ['crizotinib'] @entity1759 :: ('960', 'Gene') :: ['CD44'] @entity319 :: ('3791', 'Gene') :: ['VEGFR-2'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastases', 'metastasis'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity24197 :: ('MESH:C565455', 'Disease') :: ['KPC'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine']
@entity3 :: (MESH:D009362,Disease) :: ['Metastasis']
