A group from Department of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine, Akita, Japan, etc. has reported that lactosylceramide alpha-2,3-sialyltransferase (ST3G5) would be a suitable therapeutic target for preventing peritoneal dissemination mediated by exosomes secreted from ST3G5-high cancer cells.
https://pubmed.ncbi.nlm.nih.gov/37716915/
In this paper, the roles of lactosylceramide alpha-2,3-sialyltransferase (ST3G5; also known as ST3GAL5 and GM3 synthase) in the exosome-mediated pre-metastatic niche in peritoneal milky spots (MSs)was investigated.
It was demonstrated that exosomes secreted from ST3G5-high cancer cells (ST3G5high-cExos) were found to contain high levels of h ypoxia-inducible factor 1-alpha (HIF1α) and glycolytic enzymes, and accumulated in MSs via uptake in macrophages owing to increased expression of sialic acid binding GM3 receptor (CD169; also known as Siglec1). The upreguration of CD169 further promotes the incorporation of exosomes via positive-feedback loop.
As is known, GM3 is the first molecule in ganglioside family biosynthesisformed by the transfer of sialic acid to lactosylceramide by ST3G5 and regulates cell adhesion, proliferation, and migration, and it was shown that HIF1α increases the expression of immune checkpoint molecules, PD-L1, and T cell exhaustion in MSs
This results suggest that ST3G5 would be a promising target for preventing peritoneal dissemination in some cancers.