Biological Roles of Integrin Signal Transduction at Cell-Cell Contact in the Invasion and Metastasis of Endometrial Cancer

细胞-细胞接触整合素信号转导在子宫内膜癌侵袭和转移中的生物学作用

• 批准号: 13671727
• 负责人: MIYAMOTO Shingo
• 金额: $ 2.82万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671727/
• 关键词: CD9; CD151; Integrin; Cadherin; Endometrial Cancer; Ovarian Cancer; Signal Transduction

(1) In endometrial cancer, the loss of function of E-cadherin was associated with a decrease of E-cadherin and α-catenin expression in well differentiated adenocarcinoma and was involved in disturbance of adhesiveness as well as detachment mediated by α-catenin and IQGAP1 in poorly differentiated adenocarcinoma.(2) CD9 and integrin-a3 regulate cell-cell adhesion in epithelial cells. In endometrial cancer, the decrease of CD9 and integrain-a3 expression was significantly correlated with the grade of a tumor and metastasis of lymph nodes. The multivariated analysis disclosed that the expression of CD9 was considered as a significantly prognostic factor.These results suggested that the loss of adhesion molecules at cell contact sites plays a pivotal role in acquirement of invasive and metastatic properties in endometrial cancer.(3) In advanced ovarian cancer, we analyzed the expression of CD9 and CD151 localized at cell contact sites. The loss of CD9 expression was associated with drug resistance, and the loss of CD151 expression was significantly involved in the progression of disease. The multivariated analysis revealed that the expression of CD151 was regarded as a prognostic factors in patients with advanced ovarian cancer. These results suggested that the loss of tetraspanins at cell contact sites may contribute to molecular mechanisms for drug resistance in advanced ovarian cancer.

（1）在子宫内膜癌中，电子钙蛋白的功能丧失与良好分化的腺癌中的e-钙粘蛋白和α-catenin表达的降低有关，并且参与了粘附性的灾难，以及由α-catenin and IQGAP1介导的分离型和IQGAP1在较差的肾上腺纤维素中介导的（2）CD9-CD-2）。细胞。在子宫内膜癌中，CD9和整联蛋白-A3表达的降低与淋巴结的肿瘤和转移的等级显着相关。多变量分析揭示了CD9的表达被认为是明显的预后因素。这些结果表明，细胞接触部位的粘附分子的丧失在子宫内膜癌中侵袭性和转移性特性的获取中起着关键作用。（3）在晚期卵巢癌中，我们分析了CD9和CD151的表达。 CD9表达的丧失与耐药性有关，CD151表达的丧失显着参与疾病的进展。多变量分析表明，CD151的表达被认为是晚期卵巢癌患者的预后因素。这些结果表明，细胞接触部位的四叠酸酯丧失可能有助于晚期卵巢癌的耐药性分子机制。

项目成果

Kotaro Fukushima, Shingo Miyamoto, et al.: "Tumor Necrosis Factor α-Induced Apoptosis and Integrin Switching in Human Extravillous Tronhoblast Cell Line"Biology of Reproduction. (In Press). (2002)

Kotaro Fukushima、Shingo Miyamoto 等人：“人类绒毛外成细胞细胞系中的肿瘤坏死因子 α 诱导的细胞凋亡和整合素转换”（繁殖生物学）（2002 年）。

Yoshihiro Ohishi, Yoshinao Oda, Takeshi Uchimi, Hiroaki Kobayashi, Toshio Hirakawa, Shingo Miyamoto, et al.: "ATP-binding Cassette Superfamily Transporter Gene Expression in Human Primary Ovarian Cancer"Clinical Cancer Reserach. 8. 3767-3775 (2002)

Yoshihiro Ohishi、Yoshinao Oda、Takeshi Uchimi、Hiroaki Kobayashi、Toshio Hirakawa、Shingo Miyamoto 等人：“人类原发性卵巢癌中的 ATP 结合盒超家族转运蛋白基因表达”临床癌症研究。

Kenzo Sonoda, Shingo Miyamoto, et al.: "The Clinical Significance and Function of Tumor-Associated Antigen Rcas1"Proceedings : The 12^<th> Fukuoka International Symposium on Perinatal Medicine. 12. 66-69 (2001)

Kenzo Sonoda、Shingo Miyamoto 等人：“肿瘤相关抗原 Rcas1 的临床意义和功能”论文集：第 12 届福冈国际围产期医学研讨会。

Shingo Miyamoto, Ben-Zion Katz, et al.: "Direct Transmembrane Clustering and Cytoplasmic Dimerization of Focal Adhesion Kinase Initiates Its Tyrosine Phosphorylation"Biochimica et Biophysica Acta. 1592. 141-152 (2003)

Shingo Miyamoto、Ben-Zion Katz 等人：“粘着激酶的直接跨膜聚类和细胞质二聚化启动其酪氨酸磷酸化”Biochimica et Biophysicala Acta。

Kotaro Fukushima, Shingo Miyamoto, et al.: "Tumor Necrosis Factor α-Induced Apoptosis and Integrin Switching in Human Extravillous Trophoblast Cell Line"Biology of Reprodution. in press. (2002)

Kotaro Fukushima、Shingo Miyamoto 等人：“人类绒毛外滋养层细胞系中肿瘤坏死因子 α 诱导的细胞凋亡和整合素转换”，《生殖生物学》，出版中。