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CCN3 modulates bone turnover and is a novel regulator of skeletal metastasis.

Ouellet V, Siegel PM - J Cell Commun Signal (2012)

Bottom Line: The CCN family of proteins is composed of six secreted proteins (CCN1-6), which are grouped together based on their structural similarity.These matricellular proteins are involved in a large spectrum of biological processes, ranging from development to disease.In contrast, CCN3 is known to promote chondrocyte differentiation.

View Article: PubMed Central - PubMed

Affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Room 513, Montreal, Quebec, Canada, H3A 1A3.

ABSTRACT
The CCN family of proteins is composed of six secreted proteins (CCN1-6), which are grouped together based on their structural similarity. These matricellular proteins are involved in a large spectrum of biological processes, ranging from development to disease. In this review, we focus on CCN3, a founding member of this family, and its role in regulating cells within the bone microenvironment. CCN3 impairs normal osteoblast differentiation through multiple mechanisms, which include the neutralization of pro-osteoblastogenic stimuli such as BMP and Wnt family signals or the activation of pathways that suppress osteoblastogenesis, such as Notch. In contrast, CCN3 is known to promote chondrocyte differentiation. Given these functions, it is not surprising that CCN3 has been implicated in the progression of primary bone cancers such as osteosarcoma, Ewing's sarcoma and chondrosarcoma. More recently, emerging evidence suggests that CCN3 may also influence the ability of metastatic cancers to colonize and grow in bone.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram depicting the modular domains of CCN3. CCN3 shares a similar overall structural organization with the remaining CCN family members, including a secretory signal peptide (SP), an insulin-like growth factor binding protein domain (IGFBP), a von Willebrand factor type C domain (VWC), a Thrombospondin-1 type repeat (TSP-1) and a carboxyl-terminal domain (CT) that contains a cysteine knot. Known binding proteins are listed in black underneath the particular domain through which they interact with CCN3. Proteins denoted in grey are those for which the precise CCN3 domain responsible for the interaction remains unknown, but has been defined in other CCN family members. IGFs: Insulin-like Growth Factors, BMP: Bone Morphogenetic Protein; Rbp7: Retinol Binding Protein 7; HSPG: Heparan Sulfate Proteoglycan
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Fig1: Schematic diagram depicting the modular domains of CCN3. CCN3 shares a similar overall structural organization with the remaining CCN family members, including a secretory signal peptide (SP), an insulin-like growth factor binding protein domain (IGFBP), a von Willebrand factor type C domain (VWC), a Thrombospondin-1 type repeat (TSP-1) and a carboxyl-terminal domain (CT) that contains a cysteine knot. Known binding proteins are listed in black underneath the particular domain through which they interact with CCN3. Proteins denoted in grey are those for which the precise CCN3 domain responsible for the interaction remains unknown, but has been defined in other CCN family members. IGFs: Insulin-like Growth Factors, BMP: Bone Morphogenetic Protein; Rbp7: Retinol Binding Protein 7; HSPG: Heparan Sulfate Proteoglycan

Mentions: With one exception, all CCN family members possess an N-terminal signal peptide (SP) followed by four modular domains with homology to an insulin-like growth factor binding protein (IGFBP) domain, a von Willebrand factor type C domain (VWC), a Thrombospondin-1 type repeat (TSP-1) and a C-terminal region (CT) containing a cysteine knot structure. CCN5 is the only family member that deviates from this overall domain organization due to the absence of the CT domain (Pennica et al. 1998; Zhang et al. 1998). In each case, the VWC and TSP-1 domains are separated by a variable hinge region (Fig. 1).Fig. 1


CCN3 modulates bone turnover and is a novel regulator of skeletal metastasis.

Ouellet V, Siegel PM - J Cell Commun Signal (2012)

Schematic diagram depicting the modular domains of CCN3. CCN3 shares a similar overall structural organization with the remaining CCN family members, including a secretory signal peptide (SP), an insulin-like growth factor binding protein domain (IGFBP), a von Willebrand factor type C domain (VWC), a Thrombospondin-1 type repeat (TSP-1) and a carboxyl-terminal domain (CT) that contains a cysteine knot. Known binding proteins are listed in black underneath the particular domain through which they interact with CCN3. Proteins denoted in grey are those for which the precise CCN3 domain responsible for the interaction remains unknown, but has been defined in other CCN family members. IGFs: Insulin-like Growth Factors, BMP: Bone Morphogenetic Protein; Rbp7: Retinol Binding Protein 7; HSPG: Heparan Sulfate Proteoglycan
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368020&req=5

Fig1: Schematic diagram depicting the modular domains of CCN3. CCN3 shares a similar overall structural organization with the remaining CCN family members, including a secretory signal peptide (SP), an insulin-like growth factor binding protein domain (IGFBP), a von Willebrand factor type C domain (VWC), a Thrombospondin-1 type repeat (TSP-1) and a carboxyl-terminal domain (CT) that contains a cysteine knot. Known binding proteins are listed in black underneath the particular domain through which they interact with CCN3. Proteins denoted in grey are those for which the precise CCN3 domain responsible for the interaction remains unknown, but has been defined in other CCN family members. IGFs: Insulin-like Growth Factors, BMP: Bone Morphogenetic Protein; Rbp7: Retinol Binding Protein 7; HSPG: Heparan Sulfate Proteoglycan
Mentions: With one exception, all CCN family members possess an N-terminal signal peptide (SP) followed by four modular domains with homology to an insulin-like growth factor binding protein (IGFBP) domain, a von Willebrand factor type C domain (VWC), a Thrombospondin-1 type repeat (TSP-1) and a C-terminal region (CT) containing a cysteine knot structure. CCN5 is the only family member that deviates from this overall domain organization due to the absence of the CT domain (Pennica et al. 1998; Zhang et al. 1998). In each case, the VWC and TSP-1 domains are separated by a variable hinge region (Fig. 1).Fig. 1

Bottom Line: The CCN family of proteins is composed of six secreted proteins (CCN1-6), which are grouped together based on their structural similarity.These matricellular proteins are involved in a large spectrum of biological processes, ranging from development to disease.In contrast, CCN3 is known to promote chondrocyte differentiation.

View Article: PubMed Central - PubMed

Affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Room 513, Montreal, Quebec, Canada, H3A 1A3.

ABSTRACT
The CCN family of proteins is composed of six secreted proteins (CCN1-6), which are grouped together based on their structural similarity. These matricellular proteins are involved in a large spectrum of biological processes, ranging from development to disease. In this review, we focus on CCN3, a founding member of this family, and its role in regulating cells within the bone microenvironment. CCN3 impairs normal osteoblast differentiation through multiple mechanisms, which include the neutralization of pro-osteoblastogenic stimuli such as BMP and Wnt family signals or the activation of pathways that suppress osteoblastogenesis, such as Notch. In contrast, CCN3 is known to promote chondrocyte differentiation. Given these functions, it is not surprising that CCN3 has been implicated in the progression of primary bone cancers such as osteosarcoma, Ewing's sarcoma and chondrosarcoma. More recently, emerging evidence suggests that CCN3 may also influence the ability of metastatic cancers to colonize and grow in bone.

No MeSH data available.


Related in: MedlinePlus