Sphingosylphosphorylcholine in cancer progress

Abstract

Sphingosylphosphorylcholine (SPC) is a naturally occurring bioactive sphingolipid in blood plasma, metabolizing from the hydrolysis of the membrane sphingolipid. It has been shown to exert multifunctional role in cell physiological regulation either as an intracellular second messenger or as an extracellular agent through G protein coupled receptors (GPCRs). Because of elevated levels of SPC in malicious ascites of patients with cancer, the role of SPC in tumor progression has prompted wide interest. The factor was reported to affect the proliferation and/or migration of many cancer cells, including pancreatic cancer cells, epithelial ovarian carcinoma cells, rat C6 glioma cells, neuroblastoma cells, melanoma cells, and human leukemia cells. This review covers current knowledge of the role of SPC in tumor.

Keywords: GPCRs; Sphingosylphosphorylcholine; cancer; second messenger.

Figure 1

Effect of sphingosylphosphorylcholine (SPC) on pancreatic-cancer PANC-1 cells. SPC inhibits proliferation of PANC-1 cells by G1/S arresting and promotes PANC-1 migration dependent of Tgase or JNK-regulated phosphoralation of Keratin8 (K8).

Figure 2

SPC affects proliferation, migration, apoptosis and differentiation of cancer cells. SPC inhibits proliferation and migration of cancer cells by PI3K/AKT, MAPK, MEK/ERK/Keratin8, Tgase2/JNK/Keratin8 pathway. The Ca²⁺, p125FAK, G1/S arrest was responsible for its inhibiting proliferation, and S1P2 or other GPCRs was involved in its promoting migration. The increase of Ca²⁺ was associated with its promoting apoptosis function, and MEK/ERK was also involved in its promoting differentiation role.