Survival of salivary pleomorphic adenoma cells in hypoxic condition

缺氧条件下唾液多形性腺瘤细胞的存活

• 批准号: 22791810
• 负责人: MARUYAMA Satoshi
• 金额: $ 2.58万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791810/
• 关键词: 実験腫瘍学; 唾液腺多形性線種; 低酸素; HIF-1α; VEGF; VHL; SM-AP; perlecan; fibronectin; 唾液腺多形性腺腫; pVHL; Perlecan

Salivary pleomorphic adenoma(PA) is histopathologically characaterized by its colorful stroma with myxoid appearances, which are poorly vascularized, and PA cells are supposed to be able to survive in hypoxic conditions. To understand the hypoxia-dependent manner of cellular proliferation, we determined both protein and gene expression levels of hypoxia-inducible factor 1α(HIF-1α), vascular endothelial growth factor(VEGF), and von Hippel-Lindau(vHL), which degrades HIF-1α. SM-AP cells, which I established from a human parotid pleomorphic adenoma, showed more enhanced levels of HIF-1α, and their VEGF protein levels were kept higher in hypoxic conditions than in aerobic ones. SM-AP cells showed lower expression levels for the vHL gene. Likewise, tumor tissue masses of transplanted SM-AP cells were lower in O_2 concentration than normal subcutanous tissue. The results indicate that pleomorphic adenoma cells can proliferate in the hypoxic condition in which HIF-1αprotein levels were maintained in higher levels because the degradation of HIF-1αwas inhibited due to the lower vHL protein levels. It is thus concluded that hypoxia is more beneficial for PA cell proliferation.

涎腺多形性腺瘤（PA）的组织病理学特征是间质呈粘液样，血管化差，PA细胞被认为能在缺氧条件下存活。为了了解细胞增殖的缺氧依赖性方式，我们测定了缺氧诱导因子1α（HIF-1α）、血管内皮生长因子（VEGF）和降解HIF-1α的von Hippel-Lindau（vHL）的蛋白和基因表达水平。我从人腮腺多形性腺瘤中建立的SM-AP细胞在低氧条件下比有氧条件下显示出更高的HIF-1α水平，并且其VEGF蛋白水平保持较高。SM-AP细胞显示vHL基因的表达水平较低。同样，移植SM-AP细胞的肿瘤组织块的O_2浓度低于正常皮下组织。结果表明，在低氧条件下，由于vHL蛋白水平的降低抑制了HIF-1α的降解，从而维持了HIF-1α蛋白水平的较高水平，多形性腺瘤细胞可以在低氧条件下增殖。因此，缺氧更有利于PA细胞的增殖。

项目成果

Nuclear translocation of b-catenin synchronized with loss of E-cadherin in oral epithelial dysplasia with a characteristic two-phase appearance

具有特征性两相外观的口腔上皮发育不良中 b-连环蛋白的核转位与 E-钙粘蛋白的丢失同步

• 发表时间: 2011
• 期刊: Histopathology
• 影响因子: 6.4
• 作者: Alvarado CG;Maruyama S;Cheng J;Ida-Yonemochi H;Kobayashi T;Yamazaki M;Takagi R;Saku T
• 通讯作者: Saku T

A case of desmoplastic ameloblastoma arising in the maxillary alveolus : the origin and time-couse changes in the early stage of tumor development observed on dental radiographs

上颌牙槽促结缔组织增生性成釉细胞瘤一例：牙科X光片上观察到肿瘤发展早期的起源和时程变化

• 发表时间: 2010
• 期刊: Dentomaxillofac Radiol
• 作者: Katsura K;Maruyama S;Suzuki M;Saku T;Takagi R;Hayashi T
• 通讯作者: Hayashi T

口腔扁平上皮癌の浸潤性評価:パールカン免疫陽性間質の立体構築

口腔鳞状细胞癌侵袭性评估：基底膜免疫阳性基质的三维结构

• 发表时间: 2011
• 作者: Toshikatsu Kaburaki;Kenichi Namba;Koh-hei Sonoda;Takeshi Kezuka;Hiroshi Keino;丸山智
• 通讯作者: 丸山智

Combined immunohistochemistry for the differential diagnosis of cystic jaw lesions: its practical use in surgical pathology

• DOI: 10.1111/j.1365-2559.2010.03712.x
• 发表时间: 2010-12
• 期刊: Histopathology
• 影响因子: 6.4
• 作者: M. Tsuneki;M. Yamazaki;Jun Cheng;S. Maruyama;Takanori Kobayashi;T. Saku

唾液腺多形性腺腫における低酸素応答性増殖機構

唾液腺多形性腺瘤的缺氧反应性生长机制

• 发表时间: 2011
• 作者: Ahsan MS;Maruyma S;et al.;丸山智;丸山智;丸山智,山崎学,程君,朔敬
• 通讯作者: 丸山智,山崎学,程君,朔敬