Molecular pathological study of mechanism in malignant changes of benign odontogenic tumors

良性牙源性肿瘤恶变机制的分子病理学研究

• 批准号: 18591999
• 负责人: CHENG Jun
• 金额: $ 2.45万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591999/
• 关键词: 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

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

本研究项目的目的是研究口腔良性肿瘤继发恶变的可能分子途径，我们主要关注钙化性牙源性囊肿（COT），因为我们已经提出了钙化性牙源性囊肿可能发生恶变。为此，我们从一名 54 岁男性上颌骨钙化性牙源性囊肿中分离出 6 个细胞系统（指定为 COT1 至 COT6）。 COT1-COT6 显示出具有多边形细胞形状的牙源性上皮特征：它们对角蛋白呈免疫阳性，并表达不同的角蛋白 16、牙釉蛋白、tuftelin、BSP、MMP-20 和 ALP mRNA 水平。形成巢状结构，后期出现鬼细胞和钙化物，最后发展成钙化物。 COT6细胞巢内的结节显示，这些细胞不仅存在数量异常，例如平均数量为59条染色体的3n倍体，而且还存在各种结构异常，其中包括der(9)t(9; 13)。 )(p13.3;q12.3) 是所有六种细胞系统共有的，在裸鼠中形成具有鳞状细胞癌样外观的肿瘤。移植肿瘤细胞灶中的角化与鬼细胞分化和钙化密切相关。在 COC 手术标本中，鬼细胞对细胞外基质 (ECM) 分子（包括基底膜蛋白以及 MMP7 或 β-连环蛋白）呈阳性。细胞是由细胞质中滞留的ECM分子产生的，这些分子与Wnt信号通路有关。这些结果表明COT具有潜在的肿瘤性，并且六种COT细胞系统是研究鬼细胞分子机制的有用模型此外，研究结果表明，COT 含有癌前肿瘤细胞，这些细胞能够通过上述基因改变转化为恶性细胞。本研究首次在体外证明了良性牙源性肿瘤的继发性恶性转化。较少的

项目成果

下顎骨腫瘍

下颌骨肿瘤

• 发表时间: 2007
• 作者: Sawair FA;Cheng J;Hao N;Maruyama S;Hoshina H;Takagi R;Koyama J;Hayashi T;Saku T;Sawair FA;Kundu S;Mikami T;常木雅之;Alvarado C
• 通讯作者: Alvarado C

Immunohistochemistry for CK17 in the differential diagnosis of oral borderline malignancies.

CK17 的免疫组织化学在口腔交界性恶性肿瘤鉴别诊断中的应用。

• 发表时间: 2007
• 作者: Sawair FA;Cheng J;Hao N;Maruyama S;Hoshina H;Takagi R;Koyama J;Hayashi T;Saku T;Sawair FA;Kundu S;Mikami T
• 通讯作者: Mikami T

口腔底粘膜下腫瘍

口腔底粘膜下肿瘤

• 发表时间: 2006
• 作者: Alvarado C;et al;Carlos A;常木雅之;程 [クン]
• 通讯作者: 程 [クン]

単嚢胞性エナメル上皮腫の鑑別診断におけるケラチン分子種免疫組織化学の有効性

角蛋白分子种类免疫组织化学在单囊成釉细胞瘤鉴别诊断中的有效性

• 发表时间: 2007
• 作者: Alvarado C;et al;Carlos A;常木雅之
• 通讯作者: 常木雅之

Perlecan-rich epithelial linings as a background of proliferative potentials of keratocystic odontogenic tumor

富含基底膜的上皮衬里作为角化囊性牙源性肿瘤增殖潜力的背景

• 发表时间: 2008
• 期刊: Journal of Oral Pathology & Medicine 37
• 作者: Tsuneki M;Cheng J;Maruyama S;Ida-Yonemochi H;Nakajima M;Saku T
• 通讯作者: Saku T