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Analysis of the function of TM4SF complex and its application of lung cancer therapy.

TM4SF复合物的功能分析及其在肺癌治疗中的应用

基本信息

批准号：
16390400
负责人：
MIYAKE Masayuki
金额：
$ 8万
依托单位：
The Tazuke Kofukai
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390400/
关键词：
TM4SF AAH MRP-1 CD9 KAI1 CD82 PETA3 CD151 下位遺伝子 MRP1 VEGF-A

项目摘要

Previously, we found that MRP-1/CD9, a member of the tetraspanin family, suppressed cell motility and metastatic potential to lungs. Moreover, reduction of MRP-1/CD9 gene expression was found to be a factor of a poor prognosis for the patients with non-small cell lung cancer, as was another member of TM4SF, KAI1/CD82. On the other hand, CD151 is identical to an exciting gene PETA-3 which may promote tumor metastasis of malignant cells and its expression may be involved in the malignant progression cancer. We have established various stages of lung cancer cell lines and investigated the complex between tetraspsnin family members and integrin family members. Especially, the complex formation of MRP-1/CD9, KAI1/CD82 and PETA3/CD151 were analyzed. In the Stage I, MRP-1/CD9 and KAI1/CD82 expression were found in two cell lines except one, but PETA3/CD151 appeared weak expression. In the Stage II, KAI1/CD82 was decreasing in 5 cases and MRP-1/CD9 was decreasing in 1 case, however PETA3/CD151 was increasing in 2 cases. In the StageIII, only KAI1/CD82was found decreasing in 4 cases. Then only PETA3/CD151 was appeared in the last 1case. In the StageIV, expression of PETA3/CD151 was positive in almost all metastatic cell lines. From these experiments, MRP-1/CD9 and KAI1/CD82 play an important role as metastasis suppressor genes. On the other hand, PETA3/CD151 plays a metastasis promotion gene. Hence, the balance and unbalance of these expressions have something to do with the process of 'metastasis. Besides, we have found that MRP-1/CD9 and KAI1/CD82 regulate VEGF-A gene and Wnt-1 gene. In addition, we have established the monoclonal antibody recognizing MRP-1/CD9-integrin α3 complex. Using this antibody, we will be able to analyze the mechanism of this complex.

以前，我们发现，MRP-1/CD 9，四跨膜蛋白家族的成员，抑制细胞运动和肺转移的潜力。MRP-1/CD 9基因表达降低是非小细胞肺癌患者预后不良的一个因素，TM 4SF的另一成员KAI 1/CD 82也是如此。另一方面，CD 151与可促进恶性细胞的肿瘤转移的激动基因PETA-3相同，并且其表达可能参与恶性进展癌症。我们已经建立了不同阶段的肺癌细胞系，并研究了tetraspsnin家族成员和整合素家族成员之间的复合物。特别是分析了MRP-1/CD 9、KAI 1/CD 82和PETA 3/CD 151的复合物形成。在第I期，除1株细胞外，其余2株细胞均表达MRP-1/CD 9和KAI 1/CD 82，PETA 3/CD 151呈弱表达。Ⅱ期KAI 1/CD 82下降5例，MRP-1/CD 9下降1例，PETA 3/CD 151上升2例。Ⅲ期仅KAI 1/CD 82降低4例。后1例仅PETA 3/CD 151阳性。在IV期，PETA 3/CD 151在几乎所有转移细胞系中表达阳性。从这些实验中，MRP-1/CD 9和KAI 1/CD 82作为转移抑制基因发挥重要作用。另一方面，PETA 3/CD 151起转移促进基因的作用。因此，这些表达的平衡与失衡与“转移”的过程有关。此外，我们还发现MRP-1/CD 9和KAI 1/CD 82对VEGF-A基因和Wnt-1基因有调节作用。此外，我们还建立了识别MRP-1/CD 9-整合素α3复合物的单克隆抗体。使用这种抗体，我们将能够分析这种复合物的机制。