The Recycling Collagen Receptor uPARAP Is a Unique Mediator of Stromal Drug Delivery to Carcinoma Cells.

ABSTRACT: The genetic instability of cancer cells leads to cellular resistance against most targeted cancer drugs. Cancer-associated fibroblasts (CAF) infiltrate all carcinomas and are genetically stable. Using antibody-drug conjugates (ADC), we exploit the unique properties of a rapidly recycling endocytic receptor, uPARAP, to achieve highly efficient CAF-mediated drug delivery and killing of carcinomas. This receptor is generally not present on carcinoma cells and is only expressed in a restricted group of mesenchymal cancer cell types, which are sensitive to uPARAP-directed ADCs. However, we show that uPARAP is highly expressed in CAFs in all carcinoma types examined. This property is recapitulated in mouse xenograft carcinoma models. In these models, despite the absence of uPARAP on the carcinom

SUBMITTER: Norregaard KS 

PROVIDER: S-EPMC12757718 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature