ArticleMolecular cancer research : MCR2016
Oncofetal Chondroitin Sulfate Glycosaminoglycans Are Key Players in Integrin Signaling and Tumor Cell Motility.
Article in Molecular cancer research : MCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 71 citations in OpenAlex.
- Chondroitin sulfate shapes the unfolded protein response in osteosarcoma to sustain cancer cell survival during ER stress.Cell death & disease · 2026Article
- Dihydroartemisinin Unravels Dose-Dependent Transcriptomic Networks Orchestrating Ferroptosis and Metabolic Reprogramming in Colorectal Cancer.Current issues in molecular biology · 2026Article
- Oncofetal chondroitin sulfate positive circulating tumor cells as prognostic biomarkers in early-stage melanoma.Scientific reports · 2026Article
- Glycan Profiling Identifies Chondroitin-4-sulfate as a Biomarker for Platinum Response and Therapeutic Target in Ovarian Cancer.bioRxiv : the preprint server for biology · 2025Article
- Efficient candidate drug target discovery through proteogenomics in a Scottish cohort.Communications biology · 2025Article
- Transient CAR T cells with specificity to oncofetal glycosaminoglycans in solid tumors.EMBO molecular medicine · 2024Article
- Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate.Nature communications · 2024Article
- Dermatan Sulfate Affects the Activation of the Necroptotic Effector MLKL in Breast Cancer Cell Lines via the NFκB Pathway and Rac-Mediated Oxidative Stress.Biomolecules · 2024Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Sulfoconjugation of protein peptides and glycoproteins in physiology and diseases.Pharmacology & therapeutics · 2023Review
- Raman Spectroscopy Combined with Malaria Protein for Early Capture and Recognition of Broad-Spectrum Circulating Tumor Cells.International journal of molecular sciences · 2023Article
- Bispecific T cell-engager targeting oncofetal chondroitin sulfate induces complete tumor regression and protective immune memory in mice.Journal of experimental & clinical cancer research : CR · 2023Article
- Altered Glycosylation in Progression and Management of Bladder Cancer.Molecules (Basel, Switzerland) · 2023Review
- A novel enemy of cancer: recent investigations into protozoan anti-tumor properties.Frontiers in cellular and infection microbiology · 2023Review
- Anti-Tumor Effect of Parasitic Protozoans.Bioengineering (Basel, Switzerland) · 2022Review
- Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer.Nature communications · 2022Article
- Internalization and trafficking of CSPG-bound recombinant VAR2CSA lectins in cancer cells.Scientific reports · 2022Article
- Breast cancer circulating tumor cells with mesenchymal features-an unreachable target?Cellular and molecular life sciences : CMLS · 2022Review
- Article
- Detection of VAR2CSA-Captured Colorectal Cancer Cells from Blood Samples by Real-Time Reverse Transcription PCR.Cancers · 2021Article
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
Many tumors express proteoglycans modified with oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS), which are normally restricted to the placenta. However, the role of ofCS in cancer is largely unknown. The function of ofCS in cancer was analyzed using the recombinant ofCS-binding VAR2CSA protein (rVAR2) derived from the malaria parasite, Plasmodium falciparum We demonstrate that ofCS plays a key role in tumor cell motility by affecting canonical integrin signaling pathways. Binding of rVAR2 to tumor cells inhibited the interaction of cells with extracellular matrix (ECM) components, which correlated with decreased phosphorylation of Src kinase. Moreover, rVAR2 binding decreased migration, invasion, and anchorage-independent growth of tumor cells in vitro Mass spectrometry of ofCS-modified proteoglycan complexes affinity purified from tumor cell lines on rVAR2 columns revealed an overrepresentation of proteins involved in cell motility and integrin signaling, such as integrin-β1 (ITGB1) and integrin-α4 (ITGA4). Saturating concentrations of rVAR2 inhibited downstream integrin signaling, which was mimicked by knockdown of the core chondroitin sulfate synthesis enzymes β-1,3-glucuronyltransferase 1 (B3GAT1) and chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1). The ofCS modification was highly expressed in both human and murine metastatic lesions in situ and preincubation or early intravenous treatment of tumor cells with rVAR2 inhibited seeding and spreading of tumor cells in mice. This was associated with a significant increase in survival of the animals. These data functionally link ofCS modifications with cancer cell motility and further highlights ofCS as a novel therapeutic cancer target. IMPLICATIONS: The cancer-specific expression of ofCS aids in metastatic phenotypes and is a candidate target for therapy. Mol Cancer Res; 14(12); 1288-99. ©2016 AACR.
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