FcRn overexpression in human cancer drives albumin recycling and cell growth; a mechanistic basis for exploitation in targeted albumin-drug designs.

Journal of Controlled Release : Official Journal of the Controlled Release Society
Maja Thim LarsenKenneth A Howard

Abstract

Albumin accumulation in tumours could reflect a role of albumin in transport of endogenous nutrient cargos required for cellular growth and not just a suggested source of amino acids; a role driven by albumin engagement with its cognate cellular recycling neonatal Fc receptor. We investigate the hypothesis that albumin cellular recruitment is increased by higher human FcRn (hFcRn) expression in human cancer tissue that provides the mechanistic basis for exploitation in albumin-based drug designs engineered to optimise this process. Eight out of ten different human cancer tissue types screened for hFcRn expression by immunohistochemistry (310 samples) exhibited significantly higher hFcRn expression compared to healthy tissues. Accelerated tumour growth over 28 days in mice inoculated with hFcRn-expressing HT-29 human colorectal cancer cell xenografts, compared to CRISPR/Cas9 hFcRn-knockout HT-29, suggests a hFcRn-mediated tumour growth effect. Direct correlation between hFcRn expression and albumin recycling supports hFcRn-mediated diversion of albumin from lysosomal degradation. Two-fold increase in accumulation of fluorescent labelled high-binding hFcRn albumin, compared to wild type albumin, in luciferase MDA-MB-231-Luc-D3H2L...Continue Reading

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Citations

May 6, 2020·Cancer Medicine·Diana Cadena CastanedaValérie Gouilleux-Gruart
Jul 31, 2020·Expert Opinion on Drug Metabolism & Toxicology·Diego Pilati, Kenneth A Howard
Mar 6, 2021·Advances in Colloid and Interface Science·Aixa Aguilera-GarridoJulia Maldonado-Valderrama
Jul 11, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Imke Rudnik-Jansen, Kenneth A Howard

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