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(American Journal of Pathology. 2002;160:849-859.)
© 2002 American Society for Investigative Pathology

Regular Articles

The Expression of ccn3(nov) Gene in Musculoskeletal Tumors

Maria Cristina Manara*, Bernard Perbal{dagger}, Stefania Benini*, Rosaria Strammiello*, Vanessa Cerisano*, Stefania Perdichizzi*, Massimo Serra*, Annalisa Astolfi{ddagger}, Franco Bertoni§, Jennifer Alami, Herman Yeger, Piero Picci* and Katia Scotlandi*

From the Laboratorio di Ricerca Oncologica*
andServizio di Anatomia Patologica,§
IstitutiOrtopedici Rizzoli, Bologna, Italy; the Dipartimento di PatologiaSperimentale,{ddagger}
Sezione di Ricerca sul Cancro,Università di Bologna, Bologna, Italy; the Laboratoired’Oncologie Virale et Moléculaire,{dagger}
UFR de Biochimie, Université Paris, Paris, France; and theDepartment of Paediatric Laboratory Medicine,
Hospital for Sick Children, Toronto, Canada

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.




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