尼罗替尼
间质细胞
癌症研究
癌细胞
血管生成
癌症
PI3K/AKT/mTOR通路
生物
血小板源性生长因子受体
酪氨酸激酶抑制剂
酪氨酸激酶
细胞生长
医学
生长因子
内科学
伊马替尼
细胞生物学
受体
信号转导
生物化学
髓系白血病
作者
Mieko Onoyama,Yasuhiko Kitadai,Yuichiro Tanaka,Ryo Yuge,Kei Shinagawa,Shinji Tanaka,Wataru Yasui,Kazuaki Chayama
出处
期刊:Neoplasia
[Elsevier]
日期:2013-12-01
卷期号:15 (12): 1391-1399
被引量:30
摘要
Recent studies have revealed that PDGF plays a role in promoting progressive tumor growth in several cancers, including gastric cancer. Cancer-associated fibroblasts, pericytes, and lymphatic endothelial cells in stroma express high levels of PDGF receptor (PDGF-R); cancer cells and vascular endothelial cells do not. Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that increases the production of proteins that stimulate key cellular processes such as cell growth and proliferation, cell metabolism, and angiogenesis. In the present study, we examined the effects of PDGF-R tyrosine kinase inhibitor (nilotinib) and mTOR inhibitor (everolimus) on tumor stroma in an orthotopic nude mice model of human gastric cancer. Expression of PDGF-B and PDGF-Rβ mRNAs was associated with stromal volume. Treatment with nilotinib did not suppress tumor growth but significantly decreased stromal reactivity, lymphatic invasion, lymphatic vessel area, and pericyte coverage of tumor microvessels. In contrast, treatment with everolimus decreased tumor growth and microvessel density but not stromal reactivity. Nilotinib and everolimus in combination reduced both the growth rate and stromal reaction. Target molecule-based inhibition of cancer-stromal cell interaction appears promising as an effective antitumor therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI