Targeting the Hepatocyte Growth Factor and c-Met Signaling Axis in Bone Metastases

• Published in: International journal of molecular sciences Vol. 20; no. 2; p. 384
• Main Authors: Whang, Young Mi, Jung, Seung Pil, Kim, Meyoung-Kon, Chang, In Ho, Park, Serk In
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.01.2019; MDPI
• Subjects: Androgens; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Binding sites; bone; bone marrow; Bone Neoplasms - drug therapy; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Bone Neoplasms - secondary; c-Met and hepatocyte growth factor; c-Met protein; Cell cycle; Cell growth; Chemokines; Cloning; Disease; Disease Progression; Epidermal growth factor; Extracellular matrix; Gene amplification; Growth factors; Heparan sulfate; Heparan sulfate proteoglycans; Hepatocyte growth factor; Hepatocyte Growth Factor - metabolism; Humans; Insulin-like growth factors; Kinases; Ligands; MET protein; Metastases; Metastasis; microenvironment; Molecular Targeted Therapy; osteoblasts; Osteoblasts - drug effects; Osteoblasts - metabolism; osteoclasts; Osteoclasts - drug effects; Osteoclasts - metabolism; Phosphorylation; Prostate cancer; Protein expression; Protein-tyrosine kinase receptors; Proteins; Proteoglycans; Proto-Oncogene Proteins c-met - metabolism; Review; Roles; Signal Transduction - drug effects; Tumor Microenvironment - drug effects; Tyrosine; c-Met and hepatocyte growth factor; microenvironment; metastasis; osteoclasts; bone; osteoblasts; bone marrow
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20020384

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.