Agonistic monoclonal antibodies against the Met receptor dissect the biological responses to HGF

Maria Prat, Tiziana Crepaldi, Selma Pennacchietti, Federico Bussolino, Paolo M. Comoglio

Research output: Contribution to journalArticle

Abstract

Hepatocyte growth factor, also known as scatter factor, is a pleiotropic cytokine, which stimulates cell motility, invasion, proliferation, survival and morphogenesis, and induces the expression of specific genes by activating its receptor tyrosine kinase. In this work we have isolated, characterized and used as agonists two monoclonal antibodies (mAbs) directed against the extracellular domain of HGF receptor to investigate the requirements for receptor activation and for the different biological responses. The two mAbs display similar affinities, react with epitopes different from the hepatocyte growth factor binding site, and behave as either full or partial agonists. The full agonist mAb (DO-24) triggers all the biological effects elicited by hepatocyte growth factor, namely motility, proliferation, cell survival, invasion, tubulogenesis and angiogenesis. The partial agonist mAb (DN-30) induces only motility. Only the full agonist mAb is able to induce and sustain the expression of urokinase-type plasminogen activator receptor for prolonged periods of time, while both mAbs up-regulate the constitutive expression of urokinase-type plasminogen activator. Both mAbs activate receptor phosphorylation, which, being strictly dependent on mAb bivalence, requires receptor dimerization. Since simple receptor dimerization is not sufficient to trigger full biological responses, we propose that the region on the β chain of the receptor recognized by the full agonist mAb is crucial for optimal receptor activation.

Original languageEnglish
Pages (from-to)237-247
Number of pages11
JournalJournal of Cell Science
Volume111
Issue number2
Publication statusPublished - 1998

Keywords

  • Agonist mAb
  • Growth factor receptor
  • HGF
  • Invasive growth

ASJC Scopus subject areas

  • Cell Biology

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    Prat, M., Crepaldi, T., Pennacchietti, S., Bussolino, F., & Comoglio, P. M. (1998). Agonistic monoclonal antibodies against the Met receptor dissect the biological responses to HGF. Journal of Cell Science, 111(2), 237-247.