Malignant transformation in human chondrosarcoma cells supported by telomerase activation and tumor suppressor inactivation

James A Martin; Erin Forest; Joel A Block; Aloysius J Klingelhutz; Brent Whited; Steven Gitelis; Andrew Wilkey; Joseph A Buckwalter

Journal article

Malignant transformation in human chondrosarcoma cells supported by telomerase activation and tumor suppressor inactivation

James A Martin, Erin Forest, Joel A Block, Aloysius J Klingelhutz, Brent Whited, Steven Gitelis, Andrew Wilkey and Joseph A Buckwalter

Cell growth & differentiation, Vol.13(9), pp.397-407

09/2002

PMID: 12354749

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Abstract

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.

Bone Neoplasms - enzymology

Osteosarcoma - enzymology

Microscopy, Phase-Contrast

Neoplasm Invasiveness

Humans

Middle Aged

Bone Neoplasms - pathology

Chondroma - pathology

Chondrosarcoma - enzymology

Time Factors

Cell Transformation, Neoplastic

Cell Division

Chondrosarcoma - pathology

Adult

Telomerase - metabolism

Aged

Telomere - metabolism

Enzyme Activation

Tumor Cells, Cultured

Child

Osteosarcoma - pathology

Chondroma - enzymology

Details

Title: Subtitle: Malignant transformation in human chondrosarcoma cells supported by telomerase activation and tumor suppressor inactivation
Creators: James A Martin - Department of Orthopaedic Surgery, The University of Iowa, Iowa City, Iowa 52242, USA. james-martin@uiowa.edu
Erin Forest
Joel A Block
Aloysius J Klingelhutz
Brent Whited
Steven Gitelis
Andrew Wilkey
Joseph A Buckwalter
Resource Type: Journal article
Publication Details: Cell growth & differentiation, Vol.13(9), pp.397-407
PMID: 12354749
NLM abbreviation: Cell Growth Differ
ISSN: 1044-9523
eISSN: 2377-0732
Publisher: United States
Language: English
Date published: 09/2002
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Radiation Oncology; Injury Prevention Research Center
Record Identifier: 9984001114302771

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