The CCN Family Proteins: Modulators of Bone Development and Novel Targets in Bone-Associated Tumors

Table 1

CCN proteins in primary bone cancers.

Cancer	CCN proteins	Expression level	Experimental observation	References
Osteosarcoma	CCN1	Higher	CCN1 associates with poor prognosis, tumour stage, metastasis and mortality	[62]
			CCN1 knockdown inhibits osteosarcoma cell invasion, migration, and lung metastases	[63]
	CCN3	Higher	CCN3 expression level is associated with higher risk to develop lung metastases	[64]
	CCN4	Higher	CCN4 associates with tumor stage and enhances the migration of osteosarcoma cells by increasing MMP-2 and MMP-9 expression	[65]
Ewing's sarcoma	CCN3	Higher	CCN3 is expressed in approximately 30% of Ewing’s sarcomas and associated with lower survival rate	[64]
			High expression of CCN3 is detected in recurrences and metastases when compared to the primary tumor.	[66]
		N/A	Forced expression of CCN3 shows decreased cell proliferation while increased migration and invasion	[67]
Chondrosarcoma	CCN1	N/A	CCN1 enhances the migration of chondrosarcoma cells by increasing MMP-13 expression	[68]
	CCN2	N/A	CCN2 increases the migration through upregulating MMP-13 expression	[69]
	CCN3	N/A	CCN3 increases the migration and expression of matrix metalloproteinase MMP-13	[70]
	CCN4	N/A	CCN4 enhances the migration of chondrosarcoma cells by increasing MMP-2 expression	[71]
	CCN6	N/A	CCN6 enhances the migration of chondrosarcoma cells by increasing ICAM-1 expression	[72]