2002 CTOS Annual Meeting Posters — Medical Oncology

EXPRESION OF THE CHONDROMODULIN-1 GENE IN OSTESARCOMAS SUGGESTS THE PRESENCE OF OSTEO-CHONDRAL BIDIRECTIONAL PRECURSOR CELLS
[Abstract ID: 51]

Category: Medical Oncology

Authors: Tomoki Aoyama¹, Takeshi Okamoto¹, Koichi Nishijo¹, Tatsuya Ishibe¹, Ko Yasura¹, Takeharu Nakamata¹, Taisuke Hosaka¹, Tomitaka Nakayama¹, Takashi Nakamura¹, Junya Toguchida²

Author Institutions: ¹Department of Orthopedic Surgery Kyoto University, Japan; ²Insitute for Frontier Medical Science Kyoto University, Japan

Presenter: Tomoki Aoyama
blue@frontier.kyoto-u.ac.jp

Correspondent: Junya Toguchida
togjun@frontier.kyoto-u.ac.jp
Kyoto city Japan 606-8507
Ph: 81-75-751-4134
Fax: 81-75-751-4144

Objectives: Chondromodulin-1(ChM1) is a glycoprotein that inhibits angiogenesis and the expression is restricted to cartilage and eye. In cartilageous tumors, the expression of ChM1 was observed only in benign lesions, suggesting the role of loss of ChM expression during the malignant transformation (Hayami, et al. FEBS letter, 2001). No informaiton, so far, has demonstrated concerning the expression of ChM1 in osteosarcomas (OS), and here we report that some OS express the ChM1, which may relate to the origin of tumor cells.

Methods: Using RT-PCR, the expression of mRNA of ChM1 in 26 cases of osteosarcoma tissues and 7 lines of ostesarcoma cell lines were analyzed.

Results: The mRNA expression of the ChM1 was observed in 10 out of 26 OS, most of which were subclassified as chondroblastic OS. Among seven OS cell lines, the expression of ChM1 was observed in two, one of which was established from a chondroblastic OS. Tumors positive for the ChM1 expressed the type II and IX collagen, and aggrecan genes, as well as the osteocalcin genes, suggesting the bidirectional differentiation potential of these tumor cells. Treatment of ChM1 negative OS cell lines with 5-azadeoxy-cytidine induced the expression of the ChM1 gene in two cell lines. Bisulfite sequencing demonstrated the methylated CpG residues in the critical promoter lesion in these cell lines, which were not methylated in human normal cartilage cells.

Conclusions: These data suggest that some OSs stem from the mesenchymal cells with bidirectional potential, and epigenetic mechanisms may take a part in the process of cell fate determination.