美研究人員發(fā)現(xiàn),，特殊的復雜糖分子(多聚糖)可對乳腺癌和前列腺癌起到抑制作用,。該發(fā)現(xiàn)有助于重新理解復合糖類在癌癥中扮演的角色，為癌癥的治療指明了一個新方向,。該研究成果發(fā)表在近期的《美國國家科學院院刊》上。
美國伯納姆醫(yī)學研究所的科學家們發(fā)現(xiàn)，多聚糖能夠與層粘連蛋白結合,，并依附于α-DG細胞表面蛋白。這種結合有助于增強上皮細胞及基底膜細胞的附著力,，防止細胞轉(zhuǎn)移,。一種名為β3GnT1的酶與LARGE/LARGE2基因一起控制著綁定層粘連蛋白的多聚糖合成。β3GnT1的下調(diào)會減少多聚糖數(shù)量,，從而導致擴散性乳腺癌細胞活動能力增強,。而當研究人員迫使侵略性癌細胞表達β3GnT1時，綁定層粘連蛋白的多聚糖則會恢復,，腫瘤的形成速度也會隨之下降,。
研究小組利用抗體對正常細胞和癌細胞中α-DG及相關多聚糖的表達情況進行了分析。結果發(fā)現(xiàn),，兩種細胞中的α-DG數(shù)量相差不多,，但癌細胞中多聚糖的數(shù)量則有明顯減少。而進一步研究表明,，在前列腺癌細胞中的α-DG多聚糖越多,，癌細胞所形成的腫瘤就越小。研究小組還發(fā)現(xiàn),，通過RNA干涉阻止β3GnT1表達后,，即使LARGE過分表達，多聚糖的數(shù)量也會下降,。
該研究小組領導人福田實教授指出,，β3GnT1具有抑制腫瘤的作用，因此,，上調(diào)β3GnT1可能成為一種新型癌癥治療手段,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS July 8, 2009, doi: 10.1073/pnas.0904515106
Tumor suppressor function of laminin-binding α-dystroglycan requires a distinct β3-N-acetylglucosaminyltransferase
Xingfeng Baoa, Motohiro Kobayashib, Shingo Hatakeyamaa, Kiyohiko Angataa, Donald Gullbergc, Jun Nakayamab, Michiko N. Fukudaa and Minoru Fukudaa,1
aTumor Microenvironment Program, Cancer Research Center, Burnham Institute for Medical Research, La Jolla, CA 92037;
bDepartment of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan; and
cDepartment of Biomedicine, University of Bergen, NO-5009, Bergen, Norway
α-Dystroglycan (α-DG) represents a highly glycosylated cell surface molecule that is expressed in the epithelial cell-basement membrane (BM) interface and plays an essential role in epithelium development and tissue organization. The α-DG–mediated epithelial cell-BM interaction is often impaired in invasive carcinomas, yet roles and underlying mechanisms of such an impaired interaction in tumor progression remain unclear. We report here a suppressor function of laminin-binding glycans on α-DG in tumor progression. In aggressive prostate and breast carcinoma cell lines, laminin-binding glycans are dramatically decreased, although the amount of α-DG and β-dystroglycan is maintained. The decrease of laminin-binding glycans and consequent increased cell migration were associated with the decreased expression of β3-N-acetylglucosaminyltransferase-1 (β3GnT1). Forced expression of β3GnT1 in aggressive cancer cells restored the laminin-binding glycans and decreased tumor formation. β3GnT1 was found to be required for laminin-binding glycan synthesis through formation of a complex with LARGE, thus regulating the function of LARGE. Interaction of the laminin-binding glycans with laminin and other adhesive molecules in BM attenuates tumor cell migratory potential by antagonizing ERK/AKT phosphorylation induced by the components in the ECM. These results identify a previously undescribed role of carbohydrate-dependent cell-BM interaction in tumor suppression and its control by β3GnT1 and LARGE.
