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Malignant Transformation in Human Chondrosarcoma Cells Supported by Telomerase Activation and Tumor Suppressor Inactivation¹

Departments of Orthopaedic Surgery [J. A. M., E. F., B. W., A. W., J. A. B.] and Microbiology [A. J. K.], The University of Iowa, Iowa City, Iowa 52242, and Section of Rheumatology, Department of Internal Medicine [J. B.], Section of Medical Oncology, Department of Orthopedics [S. G.], Rush-Presbyterian-St Luke’s Medical Center, Chicago, Illinois, 60612

Human chondrosarcomas do not respond to current chemotherapies or radiation therapy, and their size and histological appearance do not reliably predict the risk of local recurrence and metastases, making selection of surgical treatment difficult. Identifying mechanisms responsible for the proliferation and invasive behavior of these tumors would be of immense clinical value. We hypothesized that telomerase expression is one of these mechanisms. We detected telomerase expression in 7 of 16 chondrosarcomas, but cells cultured from telomerase-negative chondrosarcomas acquired strong telomerase activity and lost tumor suppressor activity after their establishment in culture. These changes were associated with accelerated indefinite cell proliferation, morphological transition, and increased invasive activity, indicating that telomerase activation and loss of cell cycle control leads to the emergence of aggressive cells from chondrosarcoma cell populations. These observations may lead to better understanding of the factors responsible for malignant transformation, local recurrence, and metastases of cartilage neoplasms.

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