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CD99 acts as an oncosuppressor in osteosarcoma
Maria Cristina Manara1, Ghislaine Bernard, Pier-Luigi Lollini
1Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, 40136 Italy.
Molecular Biology of the Cell
|January 20, 2006
Summary
CD99, a molecule controlled by RUNX2 in osteoblasts, acts as a potent suppressor of malignancy in osteosarcoma. Its forced expression inhibits tumor growth, metastasis, and anoikis resistance, suggesting an antioncogenic role.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- CD99's role in osteoblast physiology is linked to the transcription factor RUNX2.
- Limited information exists on CD99's function in malignant phenotypes, especially osteosarcoma.
- CD99 expression is significantly reduced or absent in osteosarcoma cell lines and clinical samples.
Purpose of the Study:
- To investigate the role of CD99 down-regulation in osteosarcoma development and progression.
- To determine if CD99 possesses tumor-suppressive properties in osteosarcoma.
- To elucidate the molecular mechanisms underlying CD99's potential antioncogenic effects.
Main Methods:
- Analysis of CD99 expression in osteosarcoma cell lines and clinical samples.
- Forced expression of CD99 in osteosarcoma cell lines.
- Assessment of anoikis resistance, anchorage-independent growth, cell migration, and tumorigenic/metastatic potential.
- Investigation of CD99's interaction with caveolin-1 and c-Src kinase.
Main Results:
- CD99 expression is low or undetectable in osteosarcoma.
- Forced CD99 expression suppressed anoikis resistance, anchorage-independent growth, and cell migration.
- CD99 overexpression abrogated tumorigenic and metastatic abilities in vivo.
- CD99 gene transfection induced caveolin-1 up-regulation and co-localization.
- Antisense oligonucleotides targeting caveolin-1 reversed CD99's effects on migration.
Conclusions:
- CD99 acts as a potent suppressor of malignancy in osteosarcoma.
- CD99's antioncogenic role is likely mediated through caveolin-1 up-regulation and c-Src kinase inhibition.
- CD99 down-regulation may contribute to osteosarcoma development and progression.
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