美國(guó)研究人員在最新一期《自然》雜志上報(bào)告說，他們發(fā)現(xiàn),，小鼠體內(nèi)的3個(gè)基因可以幫助乳腺癌細(xì)胞突破肌體內(nèi)的天然屏障向大腦擴(kuò)散,。這為相關(guān)治療藥物和方法的研發(fā)提供了線索,。
位于美國(guó)紐約的斯隆－凱特林癌癥研究所的研究人員在一份聲明中說,，乳腺癌細(xì)胞在擴(kuò)散至大腦的過程中需要突破密集的毛細(xì)血管網(wǎng)絡(luò),。為弄清癌細(xì)胞跨越這些肌體內(nèi)天然屏障的具體分子機(jī)制，研究人員將已發(fā)生擴(kuò)散的晚期乳腺癌患者體內(nèi)的癌細(xì)胞移入實(shí)驗(yàn)鼠體內(nèi),，并從中分離出能進(jìn)入實(shí)驗(yàn)鼠大腦的癌細(xì)胞,。
研究人員經(jīng)分析發(fā)現(xiàn)，實(shí)驗(yàn)鼠體內(nèi)名為“COX2”,、“HB-EGF”和“ST6GALNAC5”的3個(gè)基因在這一過程中起到了關(guān)鍵作用,。其中，在前兩個(gè)基因的幫助下,，乳腺癌細(xì)胞具有更強(qiáng)的移動(dòng)和入侵能力,，而后一個(gè)基因則使癌細(xì)胞能長(zhǎng)時(shí)間牢固地附著在大腦的毛細(xì)血管表面，以便其向腦部進(jìn)一步滲透,。
研究人員還指出，此前他們?cè)l(fā)現(xiàn)“COX2”基因和“HB-EGF”基因可促使癌細(xì)胞向肺部擴(kuò)散,。
乳腺癌是全球女性的頭號(hào)健康“殺手”,。相關(guān)數(shù)據(jù)顯示，每年全球新增乳腺癌患者約120萬,，有50萬人死于該病,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
