Hypersialylation in Cancer: Modulation of Inflammation and Therapeutic Opportunities

Abstract

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.

Determination of cytokine regulated glycan expression by using molecularly imprinted polymers targeting sialic acid

“…IL-8 is a chemokine, functioning by attracting cells to a site of infection, and it is therefore tempting to speculate that the increased SA-MIP binding seen by the RAW264.7 cells, could be due to a regulated SA-expression in response to IL-8. The natural ligands for SA are selectins and siglecs [30] . Indeed, the rolling of cancer cells ectopically expressing the selectin ligands on endothelial cells is potentially a crucial step favoring the metastatic process in vivo [31] .…”

Sialic acid and biology of life: An introduction

“…Altered cell sialylation in cancer affects tumor cell interactions with other cells affecting cell adhesion, migration, and metastasis [357][358][359] Sialylation affects natural killer (NK) cell cytotoxicity [360]. Tumor cell hypersialylation has been observed to enable tumor cell to evade recognition by NK cells, thus escaping the immune responses.…”

“…Tumor cell hypersialylation has been observed to enable tumor cell to evade recognition by NK cells, thus escaping the immune responses. Hypersialylation of tumor cells enables it to escape the immune surveillance [358].…”

Glycosylation on Unprotected or Partially Protected Acceptors

“…Glycoconjugates play an essential role in cellular recognition, adhesion, cell‐growth regulation, cancer cell metastasis, and inflammation . The carbohydrates on the cell surface serve as anchor sites for infectious bacteria, viruses, and toxins, resulting in pathogenesis .…”

“…Glycoconjugates play an essential role in cellular recognition, adhesion, cell-growth regulation, cancer cell metastasis, and inflammation. [1][2][3][4][5][6][7] The carbohydrates on the cell surface serve as anchor sites for infectious bacteria, viruses, and toxins, resulting in pathogenesis. [8] The undoubted therapeutic potential of glycomolecules has already been proven by the development of synthetic carbohydrate-based therapeutic agents.…”