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The CCN family proteins: modulators of bone development and novel targets in bone-associated tumors

Po-Chun Chen1, Hsu-Chen Cheng2, Shun-Fa Yang3

  • 1Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan ; Department of Medical Research, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 40201, Taiwan.

Biomed Research International
|February 20, 2014
PubMed

Insights

The CCN proteins are key regulators of bone development and the bone microenvironment. Dysregulation of CCN proteins contributes to bone tumor formation and progression, making them potential therapeutic targets.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • The CCN (Cell-Cell and Nucleus) protein family comprises six secreted, matricellular proteins.
  • These proteins are characterized by four conserved modular domains and play vital roles in diverse biological processes, including skeletal development, wound healing, fibrosis, and cancer.
  • CCN proteins mediate cell signaling by interacting with integrins and heparan sulfate proteoglycans.

Purpose of the Study:

  • To review the multifaceted roles of CCN family proteins in regulating the bone microenvironment.
  • To explore the involvement of CCN proteins in skeletal development, osteogenesis, and angiogenesis.
  • To discuss the implications of CCN protein dysregulation in primary and metastatic bone tumors.

Main Methods:

  • This review synthesizes existing literature on CCN protein function in bone biology.
  • It examines signaling pathways involving integrins, BMP, VEGF, Wnt, and Notch in relation to CCN proteins.
  • The review analyzes studies linking CCN protein expression to bone tumorigenesis.

Main Results:

  • CCN proteins are critical for osteo/chondrogenesis and vasculo/angiogenesis during vertebrate development.
  • Abnormal CCN protein expression is associated with the tumorigenesis of primary bone cancers like osteosarcoma, Ewing sarcoma, and chondrosarcoma.
  • Emerging evidence suggests CCN proteins modulate the bone microenvironment, influencing the progression of metastatic bone tumors.

Conclusions:

  • CCN proteins are integral regulators of bone homeostasis and development.
  • Their aberrant expression is implicated in bone cancer development and progression.
  • CCN proteins represent promising therapeutic targets for treating primary and metastatic bone tumors.

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