ArticleOncotarget2017
Tumor antigen glycosaminoglycan modification regulates antibody-drug conjugate delivery and cytotoxicity.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Drug resistance to antibody-drug conjugates: mechanisms, challenges, and perspectives.Cancer biology & medicine · 2026Review
- Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche.Acta neuropathologica communications · 2024Article
- Article
- Mechanisms of Resistance to Antibody-Drug Conjugates.Cancers · 2023Review
- Proteoglycans: a common portal for SARS-CoV-2 and extracellular vesicle uptake.American journal of physiology. Cell physiology · 2023Review
- Emerging Roles of NDUFS8 Located in Mitochondrial Complex I in Different Diseases.Molecules (Basel, Switzerland) · 2022Review
- Picomolar fluorescent probes for compound affinity determination to carbonic anhydrase IX expressed in live cancer cells.Scientific reports · 2022Article
- Review
- Intrinsically disordered features of carbonic anhydrase IX proteoglycan-like domain.Cellular and molecular life sciences : CMLS · 2021Review
- Human carbonic anhydrases and post-translational modifications: a hidden world possibly affecting protein properties and functions.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- Biophysical Characterization of Cancer-Related Carbonic Anhydrase IX.International journal of molecular sciences · 2020Article
- Construction and Comprehensive Analysis of a ceRNA Network to Reveal Potential Novel Biomarkers for Triple-Negative Breast Cancer.Cancer management and research · 2020Article
- The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond.Cancer metastasis reviews · 2019Review
- Pro-metastatic functions of lipoproteins and extracellular vesicles in the acidic tumor microenvironment.Cancer metastasis reviews · 2019Review
- Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells.Scientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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 provide opportunities for enhanced drug delivery to hypoxic tumor cells. In support of this concept, pharmacological inhibition of glycosaminoglycan biosynthesis with xylosides significantly potentiated the internalization and cytotoxic activity of an antibody-drug conjugate (ADC) targeted at CAIX. Moreover, cells expressing glycosaminoglycan-deficient CAIX were significantly more sensitive to ADC treatment as compared with cells expressing wild-type CAIX. We find that inhibition of CAIX endocytosis is associated with an increased localization of glycosaminoglycan-conjugated CAIX in membrane lipid raft domains stabilized by caveolin-1 clusters. The association of CAIX with caveolin-1 was partially attenuated by acidosis,
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.