The effects and possible mechanism of action of apolipoprotein M on the growth of breast cancer cells

Background: To investigate the effects and mechanism of action of apolipoprotein M (ApoM) on the growth of breast cancer (BC) cells.Methods and Results: Bioinformatics, cell experiments and animal experiments were used to verify the effect of ApoM on breast cancer cell lines and breast tumor growth in vivo. ApoM expression was significantly reduced in BC tissues, and patients with lower ApoM mRNA expression had a poorer prognosis (P<0.0001). Besides, ApoM can partially inhibit the proliferative, migratory and invasive processes of BC cells. In vivo, the difference between ApoM-OE and NC groups was no significant. The level of vitamin D receptor (VDR) protein in MDA-MB-231 cells was increased by overexpression of ApoM (P<0.05), while in MCF-7 cells, VDR levels decreased (P<0.05).Conclusions: ApoM can partially inhibit the growth of BC cells. VDR may play a role, but is not the main pathway.

Apolipoprotein M—A Marker or an Active Player in Type II Diabetes?

Apolipoprotein M (apoM) is a member of the lipocalin superfamily and an important carrier of the small bioactive lipid sphingosine-1-phosphate (S1P). The apoM/S1P complex is attached to all lipoproteins, but exhibits a significant preference for high-density lipoproteins. Although apoM, S1P, and the apoM/S1P complex have been discovered more than a decade earlier, the overall function of the apoM/S1P complex remains controversial. Evidence suggests that the complex plays a role in inflammation and cholesterol metabolism and is important for maintaining a healthy endothelial barrier, regulating the turnover of triglycerides from lipoproteins, and reducing cholesterol accumulation in vessel walls. Recent studies have also addressed the role of apoM and S1P in the development of diabetes and obesity. However, limited evidence is available, and the data published so far deviates. This review discusses the specific elements indicative of the protective or harmful effects of apoM, S1P, and the apoM/S1P complex on type 2 diabetes development. Since drugs targeting the S1P system and its receptors are available and could be potentially used for treating diabetes, this research topic is a pertinent one.

Apolipoprotein M is required for the protective effects of high density lipoprotein against ischemia-induced astrocyte apoptosis

Objectives High density lipoprotein (HDL) has been reported to show protective effects against cell death. Apolipoprotein M (ApoM) in HDL can bind with sphingosine-1-phosphate (S1P) and deliver S1P to target cells. This study aimed to evaluate the effects of HDL on astrocyte apoptosis after ischemic insult and determine the role of ApoM.Methods After ApoM-associated HDL (HDLapoM+) and ApoM-depleted HDL(HDLapoM-) were separated from mouse plasma, primary cultured mouse astrocytes were chellenged with oxygen-glucose deprivation followed by recovery in presence of HDLapoM+ or HDLapoM-. mRNA and protein samples were collected for biochemical analysis.Results The addition of HDLapoM+ attenuated apoptotic cell death in the astrocytes, but HDLapoM- did not show any effect. S1P receptor 1 (S1PR1) expression was upregulated, and specific S1PR1 inhibitor or genetic knockdown of S1pr1 abolished the protective effects. In addition, activation of Akt and ERK was induced by HDLapoM+ or free S1P, and pharmacological inhibition of Akt and ERK reduced the protection of HDLapoM+.Conclusions ApoM is essential for the protective effects of HDL, which depends on S1PR1 activation and downstream activation of Akt/ERK, Thus, ApoM may be a neuroprotective component in plasma.