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The HGF/cMET signaling promotes angiogenesis in bone marrow endothelial cells

 

Multiple myeloma is a malignant blood cell cancer, and remains incurable due to the drug resistance and poor clinical response to current therapeutic strategies. The angiogenesis of multiple myeloma is reported highly correlated with tumor development, relapse, and drug resistance. Ferrucci et al. demonstrated hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (cMET) pathway plays an important role in regulation angiogenesis. Also, inhibition of this pathway, combined with two classic anti-tumor drugs, provided a marked advance in overcoming drug resistance. The article was published on Clinical Cancer Research.

 

In bone marrow endothelial cells (ECs) from patients with multiple myeloma, the expression levels of HGF, cMET, and phospho-cMET are higher than those in control ECs, with regard to both RNA and protein. HGF is an angiogenic cytokine that functions either by trigger activities of cMET and/or enhances the expression of other angiogenic factors. By using anti-HGF and anti-cMET neutralizing antibodies (Ab) to block HGF/cMET signaling, researchers found HGF/cMET pathway plays an important part in tumor development, angiogenesis and metastatic. Furthermore, the treatment of SU11274, an inhibitor of MET signaling, markedly reduces those activities in combination with one of the two anti-tumor drugs, bortezomib or lenalidomide. The findings indicates that HGF/cMET pathway may be a promising target of therapeutic strategy for multiple  myeloma patients in dealing with angiogenesis-induced drug resistance.

 

Reference:
Clin Cancer Res. 2014 Nov 15;20(22):5796-807.

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S1080 SU11274 SU11274 (PKI-SU11274) is a selective Met (c-Met) inhibitor with IC50 of 10 nM in cell-free assays, no effects on PGDFRβ, EGFR or Tie2. SU11274 induces autophagy, apoptosis and cell cycle arrest.

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c-Met