Rodrigues Emily, Macauley Matthew S
Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2G2, Canada.
Cancers (Basel). 2018 Jun 18;10(6):207. doi: 10.3390/cancers10060207.
Cell surface glycosylation is dynamic and often changes in response to cellular differentiation under physiological or pathophysiological conditions. Altered glycosylation on cancers cells is gaining attention due its wide-spread occurrence across a variety of cancer types and recent studies that have documented functional roles for aberrant glycosylation in driving cancer progression at various stages. One change in glycosylation that can correlate with cancer stage and disease prognosis is hypersialylation. Increased levels of sialic acid are pervasive in cancer and a growing body of evidence demonstrates how hypersialylation is advantageous to cancer cells, particularly from the perspective of modulating immune cell responses. Sialic acid-binding receptors, such as Siglecs and Selectins, are well-positioned to be exploited by cancer hypersialylation. Evidence is also mounting that Siglecs modulate key immune cell types in the tumor microenvironment, particularly those responsible for maintaining the appropriate inflammatory environment. From these studies have come new and innovative ways to block the effects of hypersialylation by directly reducing sialic acid on cancer cells or blocking interactions between sialic acid and Siglecs or Selectins. Here we review recent works examining how cancer cells become hypersialylated, how hypersialylation benefits cancer cells and tumors, and proposed therapies to abrogate hypersialylation of cancer.
细胞表面糖基化是动态的，并且在生理或病理生理条件下常随细胞分化而变化。癌细胞上糖基化的改变因其在多种癌症类型中的广泛存在以及最近的研究记录了异常糖基化在癌症进展的各个阶段所起的功能作用而受到关注。一种与癌症分期和疾病预后相关的糖基化变化是高唾液酸化。唾液酸水平升高在癌症中普遍存在，越来越多的证据表明高唾液酸化如何对癌细胞有利，特别是从调节免疫细胞反应的角度来看。唾液酸结合受体，如唾液酸免疫球蛋白样凝集素（Siglecs）和选择素（Selectins），很容易被癌症高唾液酸化所利用。也有越来越多的证据表明，Siglecs调节肿瘤微环境中的关键免疫细胞类型，特别是那些负责维持适当炎症环境的细胞类型。基于这些研究，出现了新的创新方法来阻断高唾液酸化的影响，即直接减少癌细胞上的唾液酸或阻断唾液酸与Siglecs或Selectins之间的相互作用。在这里，我们综述了最近的研究工作，这些研究探讨了癌细胞如何变得高唾液酸化、高唾液酸化如何使癌细胞和肿瘤受益，以及消除癌症高唾液酸化的治疗方法。
