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The Role of Semaphorin 4D in Bone Remodeling and Cancer Metastasis

Konstantinos Lontos1, Juraj Adamik1, Anastasia Tsagianni2

  • 1Hematology-Oncology Division, Department of Medicine, UPMC Hillman Cancer Center, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States.

Frontiers in Endocrinology
|July 5, 2018
PubMed

Insights

Semaphorin 4D (Sema4D) regulates bone formation and cancer progression. Blocking Sema4D shows potential for bone anabolism and cancer therapy, with clinical trials underway.

Area of Science:

  • Molecular Biology
  • Oncology
  • Bone Biology

Background:

  • Semaphorin 4D (Sema4D) is a glycoprotein involved in neural development and immune regulation.
  • Emerging roles include platelet inactivation, angiogenesis, and bone formation.
  • Sema4D inhibits osteoblast differentiation, suggesting therapeutic potential for bone conditions.

Purpose of the Study:

  • To review the role of Sema4D in bone and cancer biology.
  • To elucidate the molecular pathways, focusing on Sema4D-Plexin-B1 signaling.
  • To highlight the relevance of this signaling in the tumor microenvironment.

Main Methods:

  • Literature review of Semaphorin 4D functions.
  • Analysis of Sema4D-Plexin-B1 signaling pathways.
  • Focus on cancer cell and bone marrow microenvironment interactions.

Main Results:

  • Sema4D acts as a coupling factor inhibiting osteoblast differentiation.
  • Dysregulation of Sema4D and Plexin-B1 is implicated in cancer progression, invasion, and metastasis.
  • Sema4D-Plexin-B1 signaling mediates crosstalk between cancer cells and bone marrow.

Conclusions:

  • Targeting Sema4D may offer anabolic benefits for bone.
  • Neutralizing Sema4D presents a therapeutic strategy for cancers and neurological disorders.
  • Early clinical trials are investigating a humanized Sema4D-neutralizing antibody.
Keywords:
Plexin-B1Sema4Dcancerosteoblastsosteoclastsplexinsemaphorin 4D

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