Role of heparanase in odontogenic tumors

乙酰肝素酶在牙源性肿瘤中的作用

• 批准号: 17591910
• 负责人: NAGATSUKA Hitoshi
• 金额: $ 1.92万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591910/
• 关键词: Odontogenic tumor; Heparanase; Ameloblastoma; Immunohistochemistry; In situ hybridization; Protein expression; Cell differentiaton; Heparan sulfate; 遺伝子

Heparan sulphate proteoglycan (HSPG) are important extracellular matrix molecules that play critical roles in cell-cell and cell-matrix interactions. Most of the biological functions are conferred by the multitude of bioactive molecules sequestered on heparan sulphate sugar chains. Heparanase is a specific endoglycosidase enzyme that selectively degrades HSPG. The degradation of HSPG by heparanase can cause the release of bioactive molecules for important cellular functions in developmental and pathological processes and also the profound decrease in extracellular matrix and basement membrane integrity.HSPG were ubiquitously detected in the tooth germ with strongest intensities in the stratum intermedium cells and the dental papilla cells whereas heparanase immunoexpression was quite limited to the growing cervical loop areas. All odontogenic tumors studied, showed stronger immunoreaction to heparanase than in the tooth germ. In ameloblastoma and adenomatoid odontogenic tumor. HSPG and heparanase were localized primarily in the neoplastic epithelium without significant staining in the mature fibrous stroma while in ameloblastic fibroma; both epithelial and mesenchymal cells were reactive. In the case of ameloblastic carcinoma, the localization of HSPG shifted to the stromal tissues accompanied by strong epithelial staining to heparanase. From the results, we suggest that: 1) increased immunolocalization of heparanase molecules may be a responsible factor for the neoplastic growth of odontogenic tissues, 2) the main function of heparanase in the normal odontogenic tissue may be local modulation of HSPG and HS bound bioactive molecules, 3) the function of heparanase is locally and tightly regulated in normal tooth germ and also to some extent in benign odontogenic tumors, 4) change in localization of HSPG and increased immunoexpression of heparanase in neoplastic cells, may represent the malignant progression of ameloblastoma to ameloblastic carcinoma.

硫酸乙酰肝素蛋白聚糖（HSPG）是重要的细胞外基质分子，在细胞与细胞、细胞与基质的相互作用中起着关键作用。大多数的生物学功能是由硫酸乙酰肝素糖链上的大量生物活性分子所赋予的。乙酰肝素酶是一种选择性降解HSPG的特异性内切糖苷酶。HSPG被乙酰肝素酶降解后可导致细胞外基质和基底膜完整性的降低，HSPG在牙胚中广泛表达，在中间层细胞和牙乳头细胞中表达强度最强，而乙酰肝素酶的免疫表达仅限于生长中的牙颈环区。所有研究的牙源性肿瘤，表现出更强的免疫反应，乙酰肝素酶比在牙胚。成釉细胞瘤和牙源性腺瘤样瘤。HSPG和乙酰肝素酶主要定位于肿瘤上皮细胞中，而在成釉细胞纤维瘤中，成熟纤维间质中无显著染色;上皮细胞和间充质细胞均具有反应性。在成釉细胞癌的情况下，HSPG的本地化转移到间质组织伴随着强烈的上皮染色乙酰肝素酶。根据结果，我们建议：1）乙酰肝素酶分子的免疫定位增加可能是牙源性组织的肿瘤生长的一个负责因素，2）乙酰肝素酶在正常牙源性组织中的主要功能可能是局部调节HSPG和HS结合的生物活性分子，3）乙酰肝素酶的功能在正常牙胚中以及在一定程度上在良性牙源性肿瘤中受到局部和紧密的调节，（4）HSPG在成釉细胞瘤细胞中的定位改变和乙酰肝素酶的免疫表达增加，可能代表成釉细胞瘤向成釉细胞癌的恶性进展。

项目成果

An immunohistochemical evaluation of BMP-2,-4, osteopontin, osteocalcin and PCNA between ossifying fibromas of the jaws and peripheral cemento-ossifying fibromas on the gingiva

• DOI: 10.1016/j.oraloncology.2006.03.017
• 发表时间: 2007-04-01
• 期刊: ORAL ONCOLOGY
• 影响因子: 4.8
• 作者: Ono, Akiko;Tsukamoto, Goichi;Sasaki, Akira
• 通讯作者: Sasaki, Akira

Various immunostaining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell carcinomas

• DOI: 10.1111/j.1600-0714.2004.00227.x
• 发表时间: 2005-02-01
• 期刊: JOURNAL OF ORAL PATHOLOGY & MEDICINE
• 影响因子: 3.3
• 作者: Nagatsuka, H;Hibi, K;Nagai, N
• 通讯作者: Nagai, N

Microcystic adnexal carcinoma with mandibular bone marrow involvement : a case report with immunohistochemistry.

下颌骨骨髓受累的微囊性附件癌：免疫组织化学病例报告。

• 发表时间: 2006
• 期刊: Am J Dermatopathol. 28(6)
• 作者: T.Moriyama;T.Iida;K.Kobayashi;T.Higashi;T.Fukuoka;H.Tsumura;C.Leon;N.Suzuki;K.Inoue;C.Gachet;K.Noguchi;M.Tominaga;Nagatsuka H
• 通讯作者: Nagatsuka H

I Epigenetic alterations of BRG1 leads to cancer development through its nuclear-cytoplasmic shuttling abnormalities

I BRG1 的表观遗传改变通过其核-细胞质穿梭异常导致癌症发展

• 发表时间: 2006
• 期刊: Med Hypotheses 67(6)
• 作者: Yamazaki;H. et al.;秦 正樹;Cengiz B;Ono A;Ono A;Phuu PP;Nagatsuka H;Cengiz B;Heikinheimo K;Siar Chong Huat;Tamamura R;Ohkawa Y;Ono A;Fujiwara T;Ueyama Y;Imada T;Hata T;Gunduz E
• 通讯作者: Gunduz E

Comparison of ready-made and self-setting alginate membranes used as a barrier membrane for guided bone regeneration.

用作引导骨再生屏障膜的现成藻酸盐膜和自凝藻酸盐膜的比较。

• 发表时间: 2006
• 期刊: J Mater Sci Mater Med. 17(3)
• 作者: Kurimoto;T;et al.;Ueyama Y
• 通讯作者: Ueyama Y