The CCN3(NOV)
protein belongs to the CCN [
cysteine-rich CYR61,
connective tissue growth factor (CTGF),
nephroblastoma overexpressed gene (Nov)] family of growth regulators, sharing a strikingly conserved multimodular organization but exhibiting distinctive functional features. Although previous studies have revealed an expression of
CCN3 protein in several normal tissues, including kidney, nervous system, lung, muscle, and cartilage, less is known about its expression in
tumors. In this study, we analyzed the expression of CCN3 in musculoskeletal
tumors, using a panel of human cell lines and tissue samples. An association between CCN3 expression and
tumor differentiation was observed in
rhabdomyosarcoma and cartilage
tumors, whereas, in
Ewing's sarcoma, the expression of this
protein seemed to be associated with a higher risk to develop
metastases. CCN3 expression was found in 15 of 45
Ewing's sarcoma tissue samples. In particular, we did not observe any expression of CCN3 in the 15 primary
tumors that did not develop
metastases. In contrast, 15 of the 30 primary
tumors that developed lung and/or bone metachronous
metastases showed a high expression of the
protein (P < 0.001, Fisher's test). Our studies indicate that CCN3 is generally expressed in the cells of the musculoskeletal system. This
protein may play a role both in normal and pathological conditions. However, the regulation of CCN3 expression varies in the different
neoplasms and depends on the type of cells. Thus, as reported for other CCN genes, the
biological properties and regulation of expression of CCN3 are dependent on the cellular context and the nature of the cells in which it is produced. Further studies will help to clarify the
biological role of this
protein in musculoskeletal
neoplasms.