Role of cancer stem cells related molecules in oral squamous cell carcinoma

肿瘤干细胞相关分子在口腔鳞癌中的作用

• 批准号: 22592246
• 负责人: YAMAZAKI Hiroshi
• 金额: $ 2.91万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22592246/
• 关键词: 口腔扁平上皮癌; 癌幹細胞; 診断マーカー; 臨床腫瘍学; 癌幹細胞関連分子; 予後因子

Oral squamous cell carcinoma (OSCC) include cellular heterogeneity, as would be expected if they arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell; however, stemness molecule expression levels and distribution remain unclear. To overcome this problem, stemness molecule expressions were determined in OSCC as well as their properties and prognosis. Two chromatin regulators, Bmi-1 and Hmga2, were identified in 12 tumors region and background pair cases of OSCC by microarray. Both molecules are known to promote stem cell self-renewal by negatively regulating the expressions of Ink4a and Arf tumor suppressors. The expression levels were analyzed in 38 pair cases of OSCC by Qrt-PCR and in 91 cases of the same stage of tongue SCC. Despite a similar target, Bmi-1 protein was expressed in an early cancerous region and HMGA2 protein was expressed in a more progressed region. Likewise, Bmi1-expressing tumor had no significance with regard to overall survival (P = 0.67), while HMGA2-expressing tumors had decreased overall survival (P = 0.05). Qrt-PCR analyses also correlated with protein levels. These findings suggest that Bmi-1 is an early detection marker to distinguish cancerous from non-cancerous regions, while HMGA2 is presumed to be a tumor prognosis marker. Among our OSCC analyses, these stemness molecules expressed not so many primitive rare cells in the tumor as almost all other cells in the tumor. OSCC cells with high expression of stemness molecules should partially behave exactly like stem cells.

口腔鳞状细胞癌（OSCC）包括细胞异质性，如果它们是由失调的干细胞或祖细胞引起的，而不是突变细胞的简单克隆扩增，这是可以预期的;然而，干性分子的表达水平和分布仍然不清楚。为了克服这个问题，干性分子的表达，确定在口腔鳞状细胞癌，以及他们的性质和预后。利用基因芯片技术在12例口腔鳞癌的肿瘤区域和背景对中检测到两种染色质调节因子Bmi-1和Hmga 2。已知这两种分子通过负调节Ink 4a和Arf肿瘤抑制因子的表达来促进干细胞自我更新。应用Qrt-PCR方法检测38例口腔鳞癌组织及91例舌鳞癌组织中的表达水平。尽管有相似的靶点，但Bmi-1蛋白在早期癌区域表达，HMGA 2蛋白在更进展的区域表达。同样，表达Bmi 1的肿瘤在总生存期方面没有显著性差异（P = 0.67），而表达HMGA 2的肿瘤的总生存期降低（P = 0.05）。Qrt-PCR分析也与蛋白质水平相关。这些发现表明Bmi-1是区分癌性和非癌性区域的早期检测标记物，而HMGA 2被认为是肿瘤预后标记物。在我们的OSCC分析中，这些干细胞分子在肿瘤中表达的原始稀有细胞并不多，而几乎所有其他细胞都在肿瘤中表达。高表达干细胞性分子的口腔鳞癌细胞应该部分表现出与干细胞完全相同的行为。

项目成果

Involvement of hepatocellular carcinoma biomarker, cyclase-associated protein 2 in zebrafish body development and cancer progression

• DOI: 10.1016/j.yexcr.2012.09.013
• 发表时间: 2013-01-01
• 期刊: EXPERIMENTAL CELL RESEARCH
• 影响因子: 3.7
• 作者: Effendi, Kathryn;Yamazaki, Ken;Sakamoto, Michiie
• 通讯作者: Sakamoto, Michiie

Lung Metastases of Epithelial-Myoepithelial Carcinoma of the Parotid Gland Successfully Treated With Chemotherapy: A Case Report.

化疗成功治疗腮腺上皮肌上皮癌肺转移：病例报告。

• DOI: 10.1016/j.joms.2012.03.031
• 发表时间: 2013
• 期刊: J Oral Maxillofac Surg.
• 作者: Yamazaki H;Ota Y;Aoki T;Kaneko A
• 通讯作者: Kaneko A

Development of follicular lymphoma of the cervical lymph nodes in a postoperative patient with tongue cancer

舌癌术后患者颈部淋巴结滤泡性淋巴瘤的发生

• DOI: 10.1016/j.tripleo.2011.08.026
• 发表时间: 2012
• 期刊: Oral Surg Oral Med Oral Pathol Oral Radiol
• 作者: Yamazaki H;Nakatogawa N;Ota Y;Karakida K;Otsuru M;Kaneko A;Shirasugi Y;Kajiwara H
• 通讯作者: Kajiwara H

Xenografted Human Amniotic Membrane-Derived Mesenchymal Stem Cells Are Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes

• DOI: 10.1161/circresaha.109.205260
• 发表时间: 2010-05-28
• 期刊: CIRCULATION RESEARCH
• 影响因子: 20.1
• 作者: Tsuji, Hiroko;Miyoshi, Shunichiro;Umezawa, Akihiro
• 通讯作者: Umezawa, Akihiro

Comparison of Malignant Bone Treatments for Reuse

恶性骨治疗再利用的比较

• 发表时间: 2013
• 期刊: Surgical Science
• 作者: Yazawa M;Mori T;Kishi K
• 通讯作者: Kishi K