Targeting the hepatocyte growth factor and c-met signaling axis in bone metastases

Young Mi Whang, Seung Pil Jung, Meyoung Kon Kim, In Ho Chang, Serk In Park

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Article number384
JournalInternational journal of molecular sciences
Volume20
Issue number2
DOIs
Publication statusPublished - 2019 Jan 2

Bibliographical note

Funding Information:
This work was supported in part by the Korea University Research Grants (S.P.J. and S.I.P.), the BK21 Plus Program of the Ministry of Education of Korea (S.I.P.), the National Cancer Center of Korea (No. HA17C0040 to S.I.P.), the National Health Technology R&D Project (HI17C0710 to I.H.C.) and the National Research Foundation of Korea (Grants No. 2016R1D1A1B03933826 to Y.M.W.; 2017R1D1A1B03028103 to S.P.J.; 2018R1D1A1A02050248 to I.H.C.; and 2015R1C1A1A01051508 and 2018R1D1A1B07050329 to S.I.P.).

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Bone
  • Bone marrow
  • C-Met and hepatocyte growth factor
  • Metastasis
  • Microenvironment
  • Osteoblasts
  • Osteoclasts

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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