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Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
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Multiple myeloma cells catalyze hepatocyte growth factor (HGF) activation by secreting the serine protease

Esther P M Tjin1, Patrick W B Derksen, Hiroaki Kataoka

  • 1Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Blood
|June 3, 2004
PubMed

Insights

Multiple myeloma plasma cells activate hepatocyte growth factor (HGF) using secreted HGF-activator (HGFA). This autocatalyzation drives myeloma growth and survival, suggesting new therapeutic targets.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Multiple myeloma (MM) is a cancer of malignant plasma cells in the bone marrow.
  • Hepatocyte growth factor (HGF) is crucial for MM cell growth and survival via HGF/MET signaling.
  • Activation of HGF is a rate-limiting step in this signaling pathway.

Purpose of the Study:

  • To investigate the role of MM plasma cells in HGF activation.
  • To identify the mechanism by which MM cells promote HGF activity.
  • To explore potential therapeutic strategies targeting HGF activation in MM.

Main Methods:

  • Analysis of HGF conversion by MM plasma cells.
  • Identification and characterization of secreted HGF-activator (HGFA).
  • Use of serine protease inhibitors and neutralizing antibodies to block HGFA activity.

Main Results:

  • Malignant MM plasma cells actively convert HGF into its active form.
  • MM cells secrete HGFA, a specific serine protease for HGF activation.
  • Blocking HGFA function inhibits HGF activation catalyzed by MM cells.

Conclusions:

  • Autocatalyzation of HGF by MM cells is a key mechanism for HGF/MET-driven myeloma progression.
  • HGFA produced by MM cells plays a critical role in myeloma growth and survival.
  • Targeting HGFA represents a potential therapeutic strategy for managing multiple myeloma.

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