美国研究人员在最新一期《自然》杂志上报告说，他们发现，小鼠体内的3个基因可以帮助乳腺癌细胞突破肌体内的天然屏障向大脑扩散。这为相关治疗药物和方法的研发提供了线索。
位于美国纽约的斯隆－凯特林癌症研究所的研究人员在一份声明中说，乳腺癌细胞在扩散至大脑的过程中需要突破密集的毛细血管网络。为弄清癌细胞跨越这些肌体内天然屏障的具体分子机制，研究人员将已发生扩散的晚期乳腺癌患者体内的癌细胞移入实验鼠体内，并从中分离出能进入实验鼠大脑的癌细胞。
研究人员经分析发现，实验鼠体内名为“COX2”、“HB-EGF”和“ST6GALNAC5”的3个基因在这一过程中起到了关键作用。其中，在前两个基因的帮助下，乳腺癌细胞具有更强的移动和入侵能力，而后一个基因则使癌细胞能长时间牢固地附着在大脑的毛细血管表面，以便其向脑部进一步渗透。
研究人员还指出，此前他们曾发现“COX2”基因和“HB-EGF”基因可促使癌细胞向肺部扩散。
乳腺癌是全球女性的头号健康“杀手”。相关数据显示，每年全球新增乳腺癌患者约120万，有50万人死于该病。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature advance online publication 6 May 2009 | doi:10.1038/nature08021
Genes that mediate breast cancer metastasis to the brain
Paula D. Bos1, Xiang H.-F. Zhang1, Cristina Nadal1,7, Weiping Shu1, Roger R. Gomis1,7, Don X. Nguyen1, Andy J. Minn2, Marc J. van de Vijver3, William L. Gerald4, John A. Foekens5 & Joan Massagué1,6
1 Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
2 Department of Radiation and Cellular Oncology, and Ludwig Center for Metastasis Research, The University of Chicago, Chicago, Illinois 60637, USA
3 Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
4 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
5 Department of Medical Oncology, Erasmus MC Rotterdam, Josephine Nefkens Institute and Cancer Genomics Centre, Rotterdam, The Netherlands
6 Howard Hughes Medical Institute, Chevy Chase, Maryland 20185, USA
7 Present addresses: Institut de Malalties Hemato-Oncològiques, Hospital Clínic, 08036 Barcelona, Spain (C.N.); Oncology Programme, Institute for Research in Biomedicine, 08028 Barcelona, Spain (R.R.G.).
The molecular basis for breast cancer metastasis to the brain is largely unknown1, 2. Brain relapse typically occurs years after the removal of a breast tumour2, 3, 4, suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood–brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the 2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood–brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver5, 6, suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain7, the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood–brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions.
