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

本研究旨在探讨口腔良性肿瘤继发恶性转化的可能分子途径。我们主要关注钙化性囊性牙源性肿瘤（COT），因为我们已经提出了钙化性牙源性囊肿的恶性变化的可能性。为此，我们已经分离出六个细胞系统（指定COT 1至COT 6）的钙化牙源性囊肿发生在上颌骨的一个54岁的男性。COT 1-COT 6表现为多边形细胞的牙源性上皮特征：它们角蛋白免疫阳性，角蛋白16、釉原蛋白、tuftelin、BSP、MMP-20和ALP的mRNA表达水平不同。与成纤维细胞共培养后，COT 6细胞生长形成网状结构，后期出现影细胞和钙化物。最后，它们在COT 6细胞巢内发育成钙化结节。染色体分析表明，细胞不仅存在3 n倍体等数目异常， ...更多信息 染色体数目平均为59条，但也有各种结构异常。其中der（9）t（9; 13）（p13.3;q12.3）为6个细胞系统所共有。COT细胞在裸鼠体内形成具有鳞状细胞癌样外观的肿瘤。移植瘤细胞角化与影细胞分化和钙化密切相关。此外，在COC的手术标本中，影细胞对细胞外基质（ECM）分子（包括串珠素以及MMP 7或β-连环蛋白）呈阳性。这些结果表明，影细胞是由ECM分子滞留在细胞质中而产生的，与Wnt信号通路有关，表明COT具有潜在的肿瘤性，这6种COT细胞系统是研究影细胞分化和上皮钙化的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而转化为恶性肿瘤。本研究是第一次在体外证明继发性恶性转化的良性牙源性肿瘤。少

项目成果

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

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

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

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

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]