神经粘附分子(Neural cell adhesion molecule, NCAM)是免疫球蛋白家族中的一员,在细胞粘附和细胞通信,尤其是神经系统的生长和塑型中起重要作用。而多聚唾液酸(Polysialic acid, PSA)则是控制NCAM粘附能力形成与神经系统分化的重要因素。研究发现,多种肿瘤细胞中存在PSA以及多聚唾液酸化的神经粘附分子(PSA-NCAM)再表达的现象,预示PSA及PSA-NCAM与多种肿瘤细胞的粘附性、迁移性和侵袭性等特性密切相关,影响肿瘤细胞的生长与转移,并通过介导多种细胞信号通路影响癌症的发生与发展。文章综述了NCAM以及PSA对癌症的发生与发展、预后的作用及其功能对细胞下游信号传导的影响。
The neural cell adhesion molecule (NCAM), the member of the immunoglobulin superfamily, plays an important role in regulating cell adhesion and cell communication, particularly in nervous system wiring and plasticity. Polysialic acid, which is attached to NCAM on cell surface, is a prominent regulator of neural cell migration and differentiation during nervous system development. It has been demonstrated that PSA and PSA-NCAM were re-expressed in some malignant tumors. It was indicated that PSA and PSA-NCAM were tightly associated with cell adhesion, migration and invasion, and mediated tumor development and progression through certain cell signaling pathways. Here, we summarize the functional role of PSA, PSA-NCAM and related cell signaling pathways in tumor development, progression and prognostic.
[1] E, Vutskits L, Kiss JZ. The role of PSA-NCAM in adult neurogenesis . Adv Exp Med Biol , 2010, 663: 127- 136.
[2] L, Bose CM, Plattner F, Landmesser LT. Distinct roles of different neural cell adhesion molecule (NCAM) isoforms in synaptic maturation revealed by analysis of NCAM 180 kDa isoform-deficient mice . J Neurosci , 2004, 24(8): 1852-1864.
[3] S, Geyer H, Wuhrer M, Geyer R, Frank G, Ger-ardy-Schahn R, Zahringer U, Schachner M. Characteri-zation of N-glycans from mouse brain neural cell adhesion molecule . Glycobiology , 2001, 11(5): 373-384.
[4] JL, Rutishauser U. Roles, regulation, and mechan-ism of polysialic acid function during neural development . Biochimie , 2001, 83(7): 635-643.
[5] D, TroyII FA. Degree of polymerization (DP) of polysialic acid (polySia) on neural cell adhesion mole-cules (N-CAMS): development and application of a new strategy to accurately determine the DP of polySia chains on N-CAMS . J Biol Chem , 2005, 280(46): 38305-38316.
[6] F, Otake Y, Nakagawa T, Kawano Y, Miyahara R, Li M, Yanagihara K, Nakayama J, Fujimoto I, Ikenaka K, Wada H. Expression of polysialic acid and STX, a human polysialyltransferase, is correlated with tumor progression in non-small cell lung cancer . Cancer Res , 2000, 60(11): 3072-3080.
[7] C, Kitajima K. Disialic, oligosialic and polysialic acids: distribution, functions and related disease . J Biochem , 2013, 154(2): 115-136.
[8] S, Medrano JF. Primer on genes encoding enzymes in sialic acid metabolism in mammals . Biochimie , 2011, 93(10): 1641-1646.
[9] H, Li Y, Sun XL. Recent advances in sialic acid- focused glycomics . J Proteomics , 2012, 75(11): 3098-3112.
[10] RA, Errington RJ, Shnyder SD, Smith PJ, Patt-erson LH. Polysialyltransferase: a new target in metastatic cancer . Curr Cancer Drug Targets , 2012, 12(8): 925-939.
[11] S, Iwasaki M. Isolation of a novel glycoprotein from the eggs of rainbow trout: occurrence of disialosyl groups on all carbohydrate chains . Biochem Biophys Res Commun , 1978, 83(3): 1018-1023.
[12] J. Occurrence of unique polysialosyl carbohydrate units in glycoproteins of developing brain . J Biol Chem , 1982, 257(20): 11966-11970.
[13] U, Sato C, Matsuda T, Kitajima K. Polysialic acid in human milk - CD36 is a new member of mammalian poly-sialic acid-containing glycoprotein . J Biol Chem , 2003, 278(16): 13875-13880.
[14] S, Arany Z, Gerardy-Schahn R, Mann D, Stamatos NM. Polysialylated neuropilin-2 is expressed on the sur-face of human dendritic cells and modulates dendritic cell-T lymphocyte interactions . J Biol Chem , 2007, 282(42): 30346-30356.
[15] S, Hane M, Kitajima K, Sato C. Novel regulation of fibroblast growth factor 2 (FGF2)-mediated cell growth by polysialic acid . J Biol Chem , 2012, 287(6): 3710-3722.
[16] M, Petit D, Forestier L, Karayan-Tapon L, Maftah A, Jauberteau MO, Battu S, Gallet FP, Lalloue F. Gly-cosylation-related gene expression is linked to differen-tiation status in glioblastomas undifferentiated cells . Cancer Lett , 2011, 312(1): 24-32.
[17] L, Yuanshu W, Yanying X, Zhongfa X, Jian Y, Feng-ling W, Xianjun Q, Kokudo N, Wei T, Weixia Z, Shuxiang C. Altered mRNA expressions of sialyltransferases in human gastric cancer tissues . Med Oncol , 2012, 29(1): 84-90.
[18] MC, Langley K, Rotsch M, Havemann K, Gratzl M. NCAM: a surface marker for human small cell lung cancer cells . FEBS Lett , 1990, 267(2): 295-300.
[19] MC, Coulibaly B, Chinot O, Loundou A, Met-ellus P, Rougon G, Figarella-Branger D. Polysialic acid neural cell adhesion molecule (PSA-NCAM) is an adverse prognosis factor in glioblastoma, and regulates olig2 exp-ression in glioma cell lines . BMC Cancer , 2010, 10: 91.
[20] F, Umemura S, Yasuda M, Osamura RY. Neuroen-docrine marker expression in thyroid epithelial tumors . Endocr Pathol , 2001, 12(3): 291-300.
[21] K, Oue N, Noguchi T, Sakamoto N, Matsusaki K, Yasui W. Immunostaining of gastric cancer with neur-oendocrin
