The Ying and Yang of Ganglioside Function in Cancer

SIMPLE SUMMARY: Gangliosides, sialylated glycosphingolipids, have been found to affect cell growth as a result of their effect on signaling pathways. An increasing number of studies have shown that cells isolated from different types of cancer may overexpress a specific ganglioside(s), which can affect the interaction of specific growth factors with their receptors, thereby altering cell behavior. As more is learned about the mechanisms by which gangliosides exert their positive or negative effects, it is anticipated that it will provide the basis for the development of treatments to inhibit the proliferation and/or metastasis of cancer cells. ABSTRACT: The plethora of information about the expression of cancer cell-associated gangliosides, their role(s) in signal transduction, and their potential usefulness in the development of cancer treatments makes this an appropriate time to review these enigmatic glycosphingolipids. Evidence, reflecting the work of many, indicates that (1) expression of specific gangliosides, not generally found in high concentrations in most normal human cells, can be linked to certain types of cancer. (2) Gangliosides can affect the ability of cells to interact either directly or indirectly with growth factor receptors, thereby changing such things as a cell’s mobility, rate of proliferation, and metastatic ability. (3) Anti-ganglioside antibodies have been tested, with some success, as potential treatments for certain cancers. (4) Cancer-associated gangliosides shed into the circulation can (a) affect immune cell responsiveness either positively or negatively, (b) be considered as diagnostic markers, and (c) be used to look for recurrence. (5) Cancer registries enable investigators to evaluate data from sufficient numbers of patients to obtain information about potential therapies. Despite advances that have been made, a discussion of possible approaches to identifying additional treatment strategies to inhibit metastasis, responsible for the majority of deaths of cancer patients, as well as for treating therapy-resistant tumors, is included.