Transforming growth factor beta receptor family ligands inhibit hepatocyte growth factor synthesis and secretion from astrocytoma cells

Brain Res Mol Brain Res. 2004 Feb 5;121(1-2):146-50. doi: 10.1016/j.molbrainres.2003.11.008.

Abstract

Transforming growth factor beta (TGFbeta) and hepatocyte growth factor (HGF) promote glioma progression. Using U87human astrocytoma cells, which express TGFbeta receptors (TbetaRs), we show (1) mRNA expression of Smads (2, 3, 4), bone morphogenetic protein (BMP)- and activin-A receptors; (2) TGFbeta1 inhibits and HGF induces proliferation; (3) TGFbeta1 and activin-A equipotently inhibit HGF secretion more than BMP-2, but none alters c-Met expression. Because interfering with TbetaR signaling might nullify the beneficial inhibition of HGF secretion, activin-A should instead be considered for combination glioma therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors / genetics
  • Activin Receptors / metabolism
  • Activins / pharmacology
  • Analysis of Variance
  • Astrocytoma / metabolism*
  • Blotting, Northern
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / pharmacology
  • Bromodeoxyuridine / metabolism
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Culture Media, Conditioned / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay / methods
  • Gene Expression Regulation / drug effects*
  • Hepatocyte Growth Factor / metabolism*
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Inhibin-beta Subunits / pharmacology
  • Ligands
  • RNA, Messenger / biosynthesis
  • Receptors, Transforming Growth Factor beta / agonists*
  • Receptors, Transforming Growth Factor beta / physiology
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Smad Proteins
  • Starvation
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Culture Media, Conditioned
  • DNA-Binding Proteins
  • Ligands
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • TGFB1 protein, human
  • Trans-Activators
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • activin A
  • Activins
  • Hepatocyte Growth Factor
  • Inhibin-beta Subunits
  • Activin Receptors
  • Bromodeoxyuridine