癌症负担由壁细胞-β3-整体调节的与瘤细胞的交叉声控制
Ping-Pui Wong1, José M Muñoz-Félix2, Maruan Hijazi3
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Centre for Tumor Biology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
不仅影响血管,还影响瘤生长. 通过发送促进癌细胞存活和增殖的信号,增强了瘤扩张.
科学领域:
- 癌症学
- 细胞生物学
- 生物化学
背景情况:
- 增强的血管形成是通过营养递送促进瘤生长的已知驱动因素.
- 壁细胞在瘤生长中的作用, 独立于BV功能, 基本上被忽视了.
研究的目的:
- 调查壁细胞和β-3整合素在瘤生长中的作用.
- 阐明壁细胞影响瘤进展的分子机制.
主要方法:
- 分析与瘤大小相关的临床数据.
- 利用小鼠瘤模型 (植入和本土) 研究瘤生长动态.
- 通过生物化学测试研究壁细胞和瘤细胞中的分子信号通路.
主要成果:
- 在患者中,高百分比的壁面β- 3整合素阴性BV与瘤大小的增加相关.
- 在小鼠模型中,壁细胞β-3整合素的损失增强了瘤的生长,但没有影响BV的数量或功能.
- 壁细胞β-3整合素损失激活了FAK-p-HGFR-p-Akt-p-p65信号,增加了CXCL1,CCL2和TIMP-1的产生.
- 壁细胞衍生CCL2促进了瘤细胞MEK1-ERK1/2-ROCK2信号传递,增强了瘤细胞的存活和生长.
结论:
- 壁细胞通过β-3整合素控制的瘤信号通路来调节瘤生长.
- 这项研究揭示了一种独立于血管功能的癌症生长调节机制.
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