2002 CTOS Annual Meeting Posters — Medical Oncology

MORPHOLOGICAL AND BIOLOGICAL HETEROGENEITY OF THREE TUMORIGENIC CELL LINES DERIVED FROM A SINGLE P53-/- OSTEOBLAST-LIKE CELL LINE, MMC2
[Abstract ID: 43]

Category: Medical Oncology

Authors: Koichi Nishijo¹, Tomitaka Nakayama¹, Hiroshi Murakami¹, Tomoki Aoyama¹, Takeshi Okamoto¹, Takashi Nakamura¹, Junya Toguchida²

Author Institutions: ¹Department of Orthopaedic Surgery Kyoto University, Kyoto Prefecture, Japan; ²Institute for Frontier Medical Sciences Kyoto Univercity, Kyoto Prefecture, Japan

Presenter: Koichi Nishijo
knsjo@frontier.kyoto-u.ac.jp

Correspondent: Junya Toguchida
togjun@frontier.kyoto-u.ac.jp
Kyoto Kyoto Prefectur Japan 606-850
Ph: +81-75-751-4134
Fax: +81-75-751-4144

Objectives: We describe three tumorigenic murine cell lines, which have a p53 deficient osteoblast-like cell as a common precursor.

Methods: MMC2, p53-/- osteoblast-like cell line, was innoculated subcutaneously into athymic mice. Cells isolated from tumors were cultured in vitro. These cells were assayed for growth properties in vitro and tumorigenicity in nude mice . Expression of osteoblast-related genes were examined by Northern blotting.

Results: Tumors developed in 3 out of 8 sites, and polyclonal cell lines were established from each tumor, and designated as MMOS1, MMOS2 and MMOS3. Expression patterns of the osteoblast-related genes were correlated well with the features of the original tumors, ranging from an osteoblastic osteosarcoma (MMOS2) to tumors with scarce or no osteoid formation (MMOS1 and MMOS3). Properties as malignant cells also varied among the three cell lines. MMOS1, which showed the slowest growth in a low-serum condition, developed markedly larger tumors in vivo than the other two cell lines. MMOS3 showed the fastest growth in a low-serum condition and produced the largest number of colonies in soft agar, but did not develop lung metastases, whereas MMOS1 and MMOS2 developed lung metastases with a frequency of 30% and 50%. Because these three cell lines have a common precursor, the heterogeneity among them is clearly attributed to genetic alterations that took place during transformation process, and therefore these cell lines will be suitable materials to isolate the responsible genes.