美研究人员发现，特殊的复杂糖分子(多聚糖)可对乳腺癌和前列腺癌起到抑制作用。该发现有助于重新理解复合糖类在癌症中扮演的角色，为癌症的治疗指明了一个新方向。该研究成果发表在近期的《美国国家科学院院刊》上。
美国伯纳姆医学研究所的科学家们发现，多聚糖能够与层粘连蛋白结合，并依附于α-DG细胞表面蛋白。这种结合有助于增强上皮细胞及基底膜细胞的附着力，防止细胞转移。一种名为β3GnT1的酶与LARGE/LARGE2基因一起控制着绑定层粘连蛋白的多聚糖合成。β3GnT1的下调会减少多聚糖数量，从而导致扩散性乳腺癌细胞活动能力增强。而当研究人员迫使侵略性癌细胞表达β3GnT1时，绑定层粘连蛋白的多聚糖则会恢复，肿瘤的形成速度也会随之下降。
研究小组利用抗体对正常细胞和癌细胞中α-DG及相关多聚糖的表达情况进行了分析。结果发现，两种细胞中的α-DG数量相差不多，但癌细胞中多聚糖的数量则有明显减少。而进一步研究表明，在前列腺癌细胞中的α-DG多聚糖越多，癌细胞所形成的肿瘤就越小。研究小组还发现，通过RNA干涉阻止β3GnT1表达后，即使LARGE过分表达，多聚糖的数量也会下降。
该研究小组领导人福田实教授指出，β3GnT1具有抑制肿瘤的作用，因此，上调β3GnT1可能成为一种新型癌症治疗手段。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
