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Vol. 17, Issue 4, 1910-1921, April 2006

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CD99 Acts as an Oncosuppressor in Osteosarcoma

Maria Cristina Manara ^*, Ghislaine Bernard , Pier-Luigi Lollini , Patrizia Nanni , Monia Zuntini ^*, Lorena Landuzzi ^* , Stefania Benini ^*, Giovanna Lattanzi , Marika Sciandra ^*, Massimo Serra ^*, Mario Paolo Colombo ^||, Alain Bernard , Piero Picci ^*, and Katia Scotlandi ^*

^* Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, 40136 Italy; Unité Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 576, Hôpital de l'Archet, 06202 Nice Cedex 3, France; Sezione di Cancerologia, Dipartimento di Patologia Sperimentale, Università di Bologna, 40126 Bologna, Italy; Istituto per i Trapianti d'organo el'Immunocitologia-Consiglio Nazionale delle Ricerche, Unit of Bologna, Istituti Ortopedici Rizzoli, 40136 Bologna, Italy; and ^|| Immunotherapy and Gene Therapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy

Submitted October 21, 2005; Revised December 16, 2005; Accepted January 5, 2005
Monitoring Editor: Gerard Evan

CD99 was recently reported to be under control of the osteoblast-specific transcription factor Cbfa1 (RUNX2) in osteoblasts, suggesting a role in the phato-physiology of these cells. No extensive information is available on the role(s) of this molecule in malignant phenotype, and osteosarcoma, in particular, has never been studied. We report that in 11 different cell lines and 17 clinical samples CD99 expression is either undetectable or very low. Being expressed in the normal counterpart, we tested the hypothesis that CD99 down-regulation may have a role in osteosarcoma development and progression. CD99-forced expression in two osteosarcoma cell lines significantly reduced resistance to anoikis, inhibited growth in anchorage independence as well as cell migration, and led to abrogation of tumorigenic and metastatic ability. Therefore, the molecule acts as a potent suppressor of malignancy in osteosarcoma. CD99 gene transfection induces caveolin-1 up-regulation and the two molecules were found to colocalize on the cell surface. Treatment with antisense oligonucleotides to caveolin-1 abrogates the effects of CD99 on migration. The findings point to an antioncogenic role for CD99 in osteosarcoma, likely through the regulation of caveolin-1 and inhibition of c-Src kinase activity.

Address correspondence to: Katia Scotlandi (katia.scotlandi{at}ior.it).

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