调解乳腺癌转移到大脑的基因
Paula D Bos1, Xiang H-F Zhang, Cristina Nadal
1Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature
|May 8, 2009
概括
乳腺癌大脑转移涉及特定的分子媒介,促进血脑屏障的穿越和殖民. ST6GALNAC5被确定为一种关键的大脑特异性基转移酶,使这一过程成为可能.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 乳腺癌大脑转移是一个重要的临床挑战,分子机制尚不清楚.
- 大脑转移通常发生在初级瘤切除数年后,这意味着扩散的癌细胞获得了适应.
研究的目的:
- 为了阐明参与乳腺癌大脑转移的分子媒介.
- 确定使癌细胞扩散,血脑屏障 (BBB) 穿越和大脑殖民成为可能的特定因素.
主要方法:
- 从晚期乳腺癌患者中分离大脑偏好的转移性细胞.
- 对来自患者的细胞和临床样本的基因表达分析.
- 功能性测试,以评估已识别的基因在BBB通道和殖民化中的作用.
主要成果:
- 确定了循环氧化酶COX2 (PTGS2),EGFR连接体HBEGF和alpha2,6-sialyltransferaseST6GALNAC5作为BBB通路的媒介.
- COX2和HBEGF涉及肺和大脑转移,而ST6GALNAC5对大脑转移具有特异性.
- 乳腺癌细胞中的ST6GALNAC5表达增强了对大脑内皮细胞的附着性和BBB转移.
结论:
- 乳腺癌大脑转移利用特定的介导体进行扩散和BBB交叉.
- ST6GALNAC5,一种脑受限的基转移酶,是一种新型,通过促进癌细胞粘附和BBB通道,是大脑转移的关键驱动因素.
- 细胞表面糖化在器官特异性转移相互作用中起着关键作用.
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