Targeting the Hepatocyte Growth Factor and c-Met Signaling Axis in Bone Metastases
- PMID: 30658428
- PMCID: PMC6359064
- DOI: 10.3390/ijms20020384
Targeting the Hepatocyte Growth Factor and c-Met Signaling Axis in Bone Metastases
Abstract
Bone metastasis is the terminal stage disease of prostate, breast, renal, and lung cancers, and currently no therapeutic approach effectively cures or prevents its progression to bone metastasis. One of the hurdles to the development of new drugs for bone metastasis is the complexity and heterogeneity of the cellular components in the metastatic bone microenvironment. For example, bone cells, including osteoblasts, osteoclasts, and osteocytes, and the bone marrow cells of diverse hematopoietic lineages interact with each other via numerous cytokines and receptors. c-Met tyrosine kinase receptor and its sole ligand hepatocyte growth factor (HGF) are enriched in the bone microenvironment, and their expression correlates with the progression of bone metastasis. However, no drugs or antibodies targeting the c-Met/HGF signaling axis are currently available in bone metastatic patients. This significant discrepancy should be overcome by further investigation of the roles and regulation of c-Met and HGF in the metastatic bone microenvironment. This review paper summarizes the key findings of c-Met and HGF in the development of novel therapeutic approaches for bone metastasis.
Keywords: bone; bone marrow; c-Met and hepatocyte growth factor; metastasis; microenvironment; osteoblasts; osteoclasts.
Conflict of interest statement
The authors declare no conflict of interest.
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- None/Korea University Research Grants
- None/the BK21 Plus Program of the Ministry of Education of Korea
- HI17C0710/the Korea Health Technology R&D
- HA17C0040/the National Cancer Center of Korea
- 2016R1D1A1B03933826 to Y. M. W., 2018R1D1A1A02050248 to I. H. C, 2017R1D1A1B03028103 to S. P. J; and 2015R1C1A1A01051508 and 2018R1D1A1B07050329/the National Research Foundation of Korea
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