Role of carbonic anhydrase in proliferation and invasion of gastrointestinal tumors.

碳酸酐酶在胃肠道肿瘤增殖和侵袭中的作用。

基本信息

批准号：
15590656
负责人：
NISHIMORI Isao
金额：
$ 2.24万
依托单位：
Kochi Univasity
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590656/
关键词：
carbonic anhydrase carbonic anhydrase-related protein intestinal cell of Cajar gastrointestinal stromal tumor colon cancer lung cancer invasion proliferation マクロアレイ炭素脱水酵素炭素脱水酵素関連蛋白 CA-RP GIST

项目摘要

Among the carbonic anhydrase(CA) gene family, CA-related proteins(CA-RP) were investigated for the effect on proliferation and invasion properties of colon cancer, gastrointestinal stromal tumor(GIST), and also lung cancer.1.Ectopic expression of CA-RP VIII by cDNA transfection in the cultured colon cancer cells (Lovo) increased proliferation and invasion properties compared to wild-type Lovo, which were shown by MTT assay and by using chemotaxis chambers.2.Xenograft produced by injection of ectopically CA-RP VIII-expressed Lovo into mice (6 weeks-old female, n=5) showed increased tumor growth rate compared to that of wild-type Lovo (p<0.05).3.Immunohistochemical analysis in GIST tissue specimens (n=26) showed positive staining for CA-RP VIII in 14 cases (54%), for CA-RP X in none and for CA-RP XI in 24 cases (92%). Otherwise, intestinal cell of Cajar that has been believed to develop to GIST showed no expression of all three CA-RPs.4.Ectopic expression of CA-RP XI by cDNA transfection in the cultured GIST cells (GIST-T1) increased proliferation and invasion properties compared to wild-type GIST-T1, which were shown by MTT assay and by using chemotaxis chambers.5.Immunohistochemical analysis for expression of CA-RP VIII showed weak staining in bronchial ciliated cells in normal lung. Otherwise, 75% of squamous cell carcinoma (n=24) and 68% of adenocarcinoma (n=25) showed strong expression of CA-RP VIII, especially in the marginal area of the tumors.6.Ectopic expression of CA-RP VIII by cDNA transfection in the cultured lung cancer cells (PC9) increased proliferation property compared to wild-type PC9.These findings suggest CA-RPs VIII and XI function to enhance proliferation and invasion in gastrointestinal tumor cells. Similar results were observed in lung cancer cells, indicating that the finings is commonly observed during carcinogenesis.

在碳酸酐酶（CA）基因家族中，CA相关蛋白（CA-RP）对结肠癌、胃肠道间质瘤（GIST）和肺癌增殖和侵袭特性的影响进行了研究。1.CA相关蛋白的异位表达MTT 测定和趋化性显示，与野生型 Lovo 相比，通过 cDNA 转染培养的结肠癌细胞 (Lovo) 的 CA-RP VIII 增加了增殖和侵袭特性2.将异位 CA-RP VIII 表达的 Lovo 注射到小鼠（6 周龄雌性，n=5）中产生的异种移植物与野生型 Lovo 相比，显示肿瘤生长速度增加（p<0.05）。3 GIST 组织标本 (n=26) 的免疫组织化学分析显示，14 例 (54%) 中 CA-RP VIII 呈阳性染色，无 CA-RP X 染色，CA-RP 呈阳性十一、24例（92%）。另外，被认为发展为GIST的Cajar肠细胞未显示所有三种CA-RP的表达。4.在培养的GIST细胞（GIST-T1）中通过cDNA转染异位表达CA-RP XI增加增殖和侵袭与野生型 GIST-T1 相比，通过 MTT 测定和使用趋化室显示了这些特性。 5.CA-RP VIII 表达的免疫组织化学分析显示支气管中的弱染色正常肺中的纤毛细胞。另外，75%的鳞状细胞癌（n=24）和68%的腺癌（n=25）显示CA-RP VIII的强表达，特别是在肿瘤的边缘区域。 6. CA-RP VIII的异位表达与野生型 PC9 相比，通过 cDNA 转染培养的肺癌细胞 (PC9) 增加了增殖特性。这些发现表明 CA-RP VIII 和 XI 具有增强胃肠道肿瘤增殖和侵袭的功能细胞。在肺癌细胞中也观察到类似的结果，表明在癌变过程中经常观察到细化现象。