Characterisation of prostate cancer sialome re-engineering via CMAH transfection reveals a bystander effect that propagates Neu5Gc presentation to neighbouring cells
Sialic acids are a family of nine-carbon -keto sugars that play essential roles in human health and disease. In mammals, they are found in two main forms: N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), with interactions between Neu5Ac-containing glycans and Siglec receptors on immune cells increasingly recognised as glyco-immune checkpoints, promoting immunosuppression.…
Prostate cancer sialome characterization via CMAH transfection unveils a bystander effect that facilitates Neu5Gc presentation to neighboring cells. Sialic acids, a family of nine-carbon keto sugars, are essential in human health and disease, primarily existing as Neu5Ac and Neu5Gc in mammals. The latter is absent in humans due to CMAH gene pseudogenisation, which codes for an enzyme responsible for converting CMP-Neu5Ac into CMP-Neu5Gc.
The study focused on prostate cancer cell model LNCaP, which was re-engineered to express rat CMAH, enabling the conversion of CMP-Neu5Ac to CMP-Neu5Gc. The transfection resulted in predominant incorporation of Neu5Gc into mucin-associated O-glycans implicated in immune suppression. Sialidase treatment significantly reduced Neu5Gc expression, confirming its presentation on cell-surface glycans.
Cell-tracing experiments demonstrated the transfer of Neu5Gc to neighboring cells, unveiling a potential bystander effect capable of propagating Neu5Gc expression within the tumour microenvironment.
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