磷酸化的表皮生长因子受体在肿瘤相关的内皮细胞在人肾细胞癌是酪氨酸激酶抑制剂治疗的主要目标。

Cheryl H Baker, Maria S Pino, Isaiah J Fidler
{"title":"磷酸化的表皮生长因子受体在肿瘤相关的内皮细胞在人肾细胞癌是酪氨酸激酶抑制剂治疗的主要目标。","authors":"Cheryl H Baker,&nbsp;Maria S Pino,&nbsp;Isaiah J Fidler","doi":"10.1593/neo.06172","DOIUrl":null,"url":null,"abstract":"<p><p>We determined whether therapy for human renal cell carcinoma (HRCC) that grows in the kidney of nude mice by the specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, PKI166, is directed against phosphorylated EGFR on tumor cells or on tumor-associated endothelial cells. EGFR+/transforming growth factor alpha (TGF-alpha)- SN12-PM6 HRCC cells were transfected with full-length sense TGF-alpha cDNA or vector control. SN12-PM6 cells expressing low or high levels of TGF-alpha were implanted into the kidney of nude mice. Only tumors produced by TGF-alpha+ HRCC cells contained tumor-associated endothelial cells expressing activated EGFR. Oral administration of PKI166 produced significant therapy only in TGF-alpha+ tumors, which correlated with apoptosis of tumor-associated endothelial cells. These data suggest that the production of TGF-alpha by HRCC cells leads to the activation of EGFR on tumor-associated endothelial cells that serve as an essential target for therapy with tyrosine kinase inhibitors.</p>","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"8 6","pages":"470-6"},"PeriodicalIF":0.0000,"publicationDate":"2006-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1601465/pdf/neo0806_0470.pdf","citationCount":"22","resultStr":"{\"title\":\"Phosphorylated epidermal growth factor receptor on tumor-associated endothelial cells in human renal cell carcinoma is a primary target for therapy by tyrosine kinase inhibitors.\",\"authors\":\"Cheryl H Baker,&nbsp;Maria S Pino,&nbsp;Isaiah J Fidler\",\"doi\":\"10.1593/neo.06172\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>We determined whether therapy for human renal cell carcinoma (HRCC) that grows in the kidney of nude mice by the specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, PKI166, is directed against phosphorylated EGFR on tumor cells or on tumor-associated endothelial cells. EGFR+/transforming growth factor alpha (TGF-alpha)- SN12-PM6 HRCC cells were transfected with full-length sense TGF-alpha cDNA or vector control. SN12-PM6 cells expressing low or high levels of TGF-alpha were implanted into the kidney of nude mice. Only tumors produced by TGF-alpha+ HRCC cells contained tumor-associated endothelial cells expressing activated EGFR. Oral administration of PKI166 produced significant therapy only in TGF-alpha+ tumors, which correlated with apoptosis of tumor-associated endothelial cells. These data suggest that the production of TGF-alpha by HRCC cells leads to the activation of EGFR on tumor-associated endothelial cells that serve as an essential target for therapy with tyrosine kinase inhibitors.</p>\",\"PeriodicalId\":18888,\"journal\":{\"name\":\"Neoplasia (New York, N.Y.)\",\"volume\":\"8 6\",\"pages\":\"470-6\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2006-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1601465/pdf/neo0806_0470.pdf\",\"citationCount\":\"22\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neoplasia (New York, N.Y.)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1593/neo.06172\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neoplasia (New York, N.Y.)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1593/neo.06172","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 22

摘要

我们确定了特异性表皮生长因子受体(EGFR)酪氨酸激酶抑制剂PKI166对裸鼠肾脏中生长的人肾细胞癌(HRCC)的治疗是否针对肿瘤细胞或肿瘤相关内皮细胞上磷酸化的EGFR。转染EGFR+/转化生长因子α (tgf - α)- SN12-PM6 HRCC细胞,转染全长感tgf - α cDNA或载体对照。将表达tgf - α或低或高水平的SN12-PM6细胞植入裸鼠肾脏。只有由tgf - α + HRCC细胞产生的肿瘤含有表达活化EGFR的肿瘤相关内皮细胞。口服PKI166仅在tgf - α +肿瘤中产生显著的治疗效果,其与肿瘤相关内皮细胞的凋亡有关。这些数据表明,HRCC细胞产生tgf - α导致肿瘤相关内皮细胞上EGFR的激活,这是酪氨酸激酶抑制剂治疗的重要靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Phosphorylated epidermal growth factor receptor on tumor-associated endothelial cells in human renal cell carcinoma is a primary target for therapy by tyrosine kinase inhibitors.

We determined whether therapy for human renal cell carcinoma (HRCC) that grows in the kidney of nude mice by the specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, PKI166, is directed against phosphorylated EGFR on tumor cells or on tumor-associated endothelial cells. EGFR+/transforming growth factor alpha (TGF-alpha)- SN12-PM6 HRCC cells were transfected with full-length sense TGF-alpha cDNA or vector control. SN12-PM6 cells expressing low or high levels of TGF-alpha were implanted into the kidney of nude mice. Only tumors produced by TGF-alpha+ HRCC cells contained tumor-associated endothelial cells expressing activated EGFR. Oral administration of PKI166 produced significant therapy only in TGF-alpha+ tumors, which correlated with apoptosis of tumor-associated endothelial cells. These data suggest that the production of TGF-alpha by HRCC cells leads to the activation of EGFR on tumor-associated endothelial cells that serve as an essential target for therapy with tyrosine kinase inhibitors.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信