The Role of Non-Human Sialic Acid Neu5Gc-Containing Glycoconjugates in Human Tumors: A Review of Clinical and Experimental Evidence

被引:0
作者
Blanco, Rances [1 ]
Munoz, Juan P. [2 ]
机构
[1] Ave Vicuna Mackenna Poniente 6315, La Florida 8240000, Chile
[2] Univ Tarapaca, Fac Ciencias, Dept Quim, Lab Bioquim, Arica 1000007, Chile
关键词
N-glycolylneuraminic acid; Neu5Gc; Neu5Gc-GM3; ganglioside; sialic acid; cancer; N-GLYCOLYLNEURAMINIC ACID; HANGANUTZIU-DEICHER ANTIGEN; CELL LUNG-CANCER; GLYCOLYL GM3 GANGLIOSIDE; BREAST-CANCER; NEUGCGM3; GANGLIOSIDE; PROGNOSTIC-SIGNIFICANCE; ACETYLNEURAMINIC ACID; DENDRITIC CELLS; MELANOMA-CELLS;
D O I
10.3390/biom15020253
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid variant commonly found in most mammals but not synthesized by humans due to an inactivating mutation in the CMP-Neu5Ac hydroxylase (CMAH) gene. Despite this, Neu5Gc-containing molecules are consistently detected in human tissues, particularly in malignant tumors. However, the mechanisms underlying Neu5Gc accumulation and its role in cancer development remain poorly understood. Objectives: This review aims to analyze clinical and experimental evidence regarding the presence of Neu5Gc-containing glycoconjugates in both tumor and non-tumor human tissues, exploring potential mechanisms of the Neu5Gc expression and evaluating its contribution to tumor biology, with a particular focus on the Neu5Gc-GM3 ganglioside. Methods: A comprehensive review of the literature was conducted, integrating findings from immunohistochemistry, chromatography, and molecular studies to assess the expression and implications of Neu5Gc in cancer biology. Results: Neu5Gc-containing glycoconjugates were found to preferentially accumulate in various malignant tumors, while their presence in normal tissues was restricted to cells with high turnover rates. This accumulation is potentially mediated by dietary uptake, hypoxic conditions, and metabolic alterations in cancer cells. Additionally, Neu5Gc-containing molecules were associated with the activation of oncogenic pathways. Conclusion: Neu5Gc-containing glycoconjugates play a multifaceted role in cancer progression and present potential as prognostic markers and therapeutic targets.
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页数:18
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  • [1] Traving C., Schauer R., Structure, function and metabolism of sialic acids, Cell Mol. Life Sci, 54, pp. 1330-1349, (1998)
  • [2] Angata T., Varki A., Chemical diversity in the sialic acids and related alpha-keto acids: An evolutionary perspective, Chem. Rev, 102, pp. 439-469, (2002)
  • [3] Pinho S.S., Reis C.A., Glycosylation in cancer: Mechanisms and clinical implications, Nat. Rev. Cancer, 15, pp. 540-555, (2015)
  • [4] Muchmore E.A., Milewski M., Varki A., Diaz S., Biosynthesis of N-glycolyneuraminic acid. The primary site of hydroxylation of N-acetylneuraminic acid is the cytosolic sugar nucleotide pool, J. Biol. Chem, 264, pp. 20216-20223, (1989)
  • [5] Collins B.E., Yang L.J., Mukhopadhyay G., Filbin M.T., Kiso M., Hasegawa A., Schnaar R.L., Sialic acid specificity of myelin-associated glycoprotein binding, J. Biol. Chem, 272, pp. 1248-1255, (1997)
  • [6] Hayashi N., Chiba H., Kuronuma K., Go S., Hasegawa Y., Takahashi M., Gasa S., Watanabe A., Hasegawa T., Kuroki Y., Et al., Detection of N-glycolyated gangliosides in non-small-cell lung cancer using GMR8 monoclonal antibody, Cancer Sci, 104, pp. 43-47, (2013)
  • [7] Rodrigues E., Macauley M.S., Hypersialylation in Cancer: Modulation of Inflammation and Therapeutic Opportunities, Cancers, 10, (2018)
  • [8] Varki A., Schauer R., Sialic acids, Essentials of Glycobiology, (2009)
  • [9] Hugonnet M., Singh P., Haas Q., von Gunten S., The Distinct Roles of Sialyltransferases in Cancer Biology and Onco-Immunology, Front. Immunol, 12, (2021)
  • [10] Sakuma K., Aoki M., Kannagi R., Transcription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced epithelial-mesenchymal transition, Proc. Natl. Acad. Sci. USA, 109, pp. 7776-7781, (2012)