The Cancer-Associated Antigens Sialyl Lewis<sup>a/x</sup> and Sd<sup>a</sup>: Two Opposite Faces of Terminal Glycosylation
Terminal carbohydrate structures are particularly relevant in oncology because they can serve as cancer markers and alter the phenotype of cancer cells. The Sd<sup>a</sup> antigen and the sialyl Lewis<sup>x</sup> and sialyl Lewis<sup>a</sup> (sLe<sup>x</s...
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| Autores principales: | , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/a1262b217fdb4a2f87b5aef2c33b7823 |
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| Sumario: | Terminal carbohydrate structures are particularly relevant in oncology because they can serve as cancer markers and alter the phenotype of cancer cells. The Sd<sup>a</sup> antigen and the sialyl Lewis<sup>x</sup> and sialyl Lewis<sup>a</sup> (sLe<sup>x</sup> and sLe<sup>a</sup>) antigens are terminal structures whose biosynthesis is mutually exclusive. In this review, we describe the main features of the Sd<sup>a</sup> antigen in cancer and its relationship with sLe<sup>x/a</sup> antigens. Information was obtained from an extensive literature search and from The Cancer Genome Atlas (TCGA) public database. The Sd<sup>a</sup> biosynthetic enzyme <i>B4GALNT2</i> undergoes downregulation in colorectal (CRC) and stomach cancer, while it is ectopically expressed by a minority of breast cancer (BRCA) patients. High expression of <i>B4GALNT2</i> is associated with better prognosis and a less malignant gene expression profile in CRC, while the opposite occurs in BRCA. The regulation of <i>B4GALNT2</i> expression in CRC is multifactorial, involving gene methylation and miRNA expression. Forced expression of <i>B4GALNT2</i> inhibited sLe<sup>a</sup>/sLe<sup>x</sup> and reduced malignancy and stemness in cells constitutively expressing sLe<sup>x/a</sup> antigens. However, consistent effects were observed upon <i>B4GALNT2</i> forced expression and in cells not expressing sLe<sup>x/a</sup> antigens. Thus, <i>B4GALNT2</i> and the Sd<sup>a</sup> antigen exert a tumor-restraining activity in CRC and probably other gastrointestinal cancers, independently of sLe<sup>x/a</sup> antigens. |
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