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

Figure 1

CCN family proteins involved in tumor metastasis and the mechanism of CCN3-modulated osteolytic bone metastasis. Tumors secrete different CCN proteins in prostate cancer (such as CCN1, CCN3, and CCN4) or breast cancer (such as CCN1, CCN2, CCN3, and CCN6) that regulate tumor metastasis. When tumor cells metastasize to the bone microenvironment, the secreted CCN protein (such as CCN3) promotes osteolytic bone metastasis in bone microenvironment through 3 different mechanisms. (a) CCN3 directly enhances osteoclasts formation through upregulating RANK expression, the crucial regulator of osteoclastogenesis. (b) CCN3 indirectly enhances osteoclast formation through affecting the RANKL/OPG secretion in osteoblasts, and the higher RANKL/OPG ratio increases the osteoclastogenesis. (c) CCN3 inhibits osteoblasts differentiation and thus reduces bone formation.