Molecular Regulation of Bone Metastasis Pathogenesis

Cell Physiol Biochem. 2018;46(4):1423-1438. doi: 10.1159/000489184. Epub 2018 Apr 18.

Abstract

Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions. Studies support the idea that distant metastases may occur due to the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). These cells inhibit T cells and natural killer (NK) cells and differentiate into tumor-associating macrophages (TAMs), monocytes, and dendritic cells (DCs). In this review, we summarize studies focusing on the role of MDSCs in bone metastasis and provide a strong foundation for developing anticancer immune treatments and anticancer therapies, in general.

Keywords: Bone metastasis; Myeloid-derived suppressor cells; Osteoblast; Osteoclast; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Bone Neoplasms / immunology
  • Bone Neoplasms / pathology*
  • Bone Neoplasms / therapy
  • Bone Remodeling
  • Cell Adhesion Molecules / metabolism
  • Cytokines / metabolism
  • Humans
  • Immune System
  • Myeloid-Derived Suppressor Cells / cytology
  • Myeloid-Derived Suppressor Cells / metabolism
  • Neoplasm Metastasis*
  • Tumor Microenvironment
  • Wnt Signaling Pathway

Substances

  • Cell Adhesion Molecules
  • Cytokines