The sphingolipids change in exosomes from cancer patients and association between exosome release and sphingolipids level based on a pseudotargeted lipidomics method

Anal Chim Acta. 2024 May 29;1305:342527. doi: 10.1016/j.aca.2024.342527. Epub 2024 Mar 25.ABSTRACTThe lipid based ESCRT-independent mechanism, which contributes to MVB formation, is one of the crucial procedures in exosome biogenesis. n-SMase is a key lipid metabolism enzyme in this mechanism and can induce the hydrolysis of sphingomyelins (SMs) to ceramides (Cers), thereby promoting the formation of ILVs inside MVBs. Therefore, the regulation of n-SMase can realize the alteration in exosome release. According to the fact that cancer-associated cells have a tendency to release more exosomes than healthy cells, lipid extracts in exosomes from healthy volunteers, HCC and ICC patients were analyzed by a novel pseudotargeted lipidomics method focused on sphingolipids (SLs) to explore whether cancer-related features regulate the release of exosomes through the above pathway. Multivariate analysis based on the SLs expression could distinguish three groups well indicated that the SLs expression among the three groups were different. In cancer groups, two species of critical Cers were up-regulated, denoted as Cer (d18:1_16:0) and Cer (d18:1_18:0), while 55 kinds of SLs were down-regulated, including 40 species of SMs, such as SM (d18:1_16:0), SM (d18:1_18:1) and SM (d18:1_24:0). Meanwhile, several species of SM/Cer exhibited significant down-regulation. This substantial enhancement of the SMs hydrolysis to Cers process during exosome biogenesis suggested that cancer-related features ...
Source: Analytica Chimica Acta - Category: Chemistry Authors: Source Type: research