title: The expression of ccn3(nov) gene in musculoskeletal tumors.
abstract: 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.
authors.affiliation: Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Manara
authors.forename: Bernard
authors.initials: B
authors.lastname: Perbal
authors.forename: Stefania
authors.initials: S
authors.lastname: Benini
authors.forename: Rosaria
authors.initials: R
authors.lastname: Strammiello
authors.forename: Vanessa
authors.initials: V
authors.lastname: Cerisano
authors.forename: Stefania
authors.initials: S
authors.lastname: Perdichizzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Serra
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.forename: Franco
authors.initials: F
authors.lastname: Bertoni
authors.forename: Jennifer
authors.initials: J
authors.lastname: Alami
authors.forename: Herman
authors.initials: H
authors.lastname: Yeger
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.forename: Katia
authors.initials: K
authors.lastname: Scotlandi
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics*; D055513:Connective Tissue Growth Factor; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D055514:Nephroblastoma Overexpressed Protein; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D012208:Rhabdomyosarcoma / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: C526317:CCN2 protein, human; C526319:CCN3 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D055513:Connective Tissue Growth Factor