Molecular pathological study of mechanism in malignant changes of benign odontogenic tumors
| Project/Area Number |
18591999
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Niigata University |
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Principal Investigator |
CHENG Jun Niigata University, Institute of Medicine and Dentistry, Associate Professor (40207460)
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| Co-Investigator(Kenkyū-buntansha) |
SATOSHI Maruyama Niigata University, Institute of Medicine and Dentistry, Assistant Professor (30397161)
TAKASHI Saku Niigata University, Institute of Medicine and Dentistry, Professor (40145264)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | calcifying cystic odontogenic tumor / cell culture / odontogenic epithelium / extracellular matrix / calcification / immunocytochemistry / RT-PCR / gene mutation / 顎骨石灰化歯原性腫瘍 / 歯原性上皮マーカ / 石灰化関連分子 / 免疫細胞化学 |
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| Research Abstract |
This research project was carried out in order to study a possible molecular pathway of secondary malignant transformation from oral benign tumors. We mainly focused on calcifying cystic odontogenic tumor (COT), because we had already proposed a possible of malignant changes within calcifying odontogenic cyst. To this end, we have isolated six cell systems (designated COT1 to COT6) from a calcifying odontogenic cyst arising in the maxilla of a 54 year-old male. COT1-COT6 showed odontogenic epithelial characteristics with polygonal cell shapes: they were immunopositive for keratin and expressed distinct mRNA levels for keratin 16, amelogenin, tuftelin, BSP, MMP-20, and ALP. In co-cultures with fibroblasts, COT6 cells grew to form nestic structures, in which ghost cells and calcified materials appeared in the later stage. Finally, they developed into calcified nodules within the COT6 cell nests. Chromosome analyses showed the cells had not only numeral abnormalities such as 3n ploidies w
… More
ith average numbers of 59 chromosomes but also various kinds of structural abnormalities. Among them, der(9)t(9; 13)(p13.3;q12.3) was shared by all of the six cell systems. COT cells formed tumors with a squamous cell carcinoma-like appearance in nude mice. Keratinization in transplanted tumor cell foci was closely associated with ghost cell differentiation and calcification. Also in surgical specimens of COC, ghost cells were positive for extracellular matrix (ECM) molecules including perlecan as well as MMP7 or β-catenin. The results indicated that ghost cells were generated by cytoplasmic retention of ECM molecules, which were related to Wnt signaling pathways.
These results show that COT is potentially neoplastic, and that the six COT cell systems are useful models for investigating the molecular mechanisms of ghost cell differentiation and epithelial calcification. In addition, the findings suggest that COT contains precancerous tumor cells which are able to transform into malignant with above mentioned gene alterations. The present study is the first in-vitro demonstration of secondary malignant transformation from a benign odontogenic tumor. Less
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Report
(3 results)
Research Products
(22 results)
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[Presentation] 下顎骨腫瘍2007
Author(s)
Alvarado C
Organizer
第18回日本口腔病理学会総会
Place of Presentation
岐阜市
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] 口腔底粘膜下腫瘍2006
Author(s)
程 [クン]
Organizer
第17回日本口腔病理学会総会
Place of Presentation
新潟市
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] 口蓋腫瘍2006
Author(s)
程 [クン]
Organizer
第63回日本病理学会東北支部総会
Place of Presentation
新潟市
Description
「研究成果報告書概要(和文)」より
Related Report
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