Tumor antigen glycosaminoglycan modification regulates antibody-drug conjugate delivery and cytotoxicity.

ABSTRACT: Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains. We show that perturbed glycosaminoglycan modification results in increased CAIX endocytosis. We hypothesized that perturbation of CAIX glycosaminoglycan conjugation may prov

SUBMITTER: Christianson HC 

PROVIDER: S-EPMC5620149 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature