ArticleThe Journal of biological chemistry2008
Combinatorial targeting of the macropinocytotic pathway in leukemia and lymphoma cells.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Targeting Non-Apoptotic Pathways with the Cell Permeable TAT-Conjugated NOTCH1 RAM Fragment for Leukemia and Lymphoma Cells.ACS omega · 2024Article
- A Tumor Homing Peptide-Linked Arsenic Compound Inhibits Pancreatic Cancer Growth and Enhances the Inhibitory Effect of Gemcitabine.International journal of molecular sciences · 2024Article
- Advancements in Chronic Myeloid Leukemia detection: Development and evaluation of a novel QCM aptasensor for use in clinical practice.Biochemistry and biophysics reports · 2024Article
- Molecular Modeling of Single- and Double-Hydrocarbon-Stapled Coiled-Coil Inhibitors against Bcr-Abl: Toward a Treatment Strategy for CML.The journal of physical chemistry. B · 2024Article
- Computational Modeling of Stapled Coiled-Coil Inhibitors Against Bcr-Abl: Toward a Treatment Strategy for CML.bioRxiv : the preprint server for biology · 2023Article
- Article
- Real-time deformability cytometry reveals sequential contraction and expansion during neutrophil priming.Journal of leukocyte biology · 2019Article
- Phage Display Libraries: From Binders to Targeted Drug Delivery and Human Therapeutics.Molecular biotechnology · 2019Review
- The pervasiveness of macropinocytosis in oncological malignancies.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- Alterations in Cellular Processes Involving Vesicular Trafficking and Implications in Drug Delivery.Biomimetics (Basel, Switzerland) · 2018Review
- Article
- Targeting Tumors with Small Molecule Peptides.Current cancer drug targets · 2016Review
- Leveraging growth factor induced macropinocytosis for targeted treatment of lung cancer.Medical oncology (Northwood, London, England) · 2015Article
- A coiled-coil mimetic intercepts BCR-ABL1 dimerization in native and kinase-mutant chronic myeloid leukemia.Leukemia · 2015Article
- Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Folding graft copolymer with pendant drug segments for co-delivery of anticancer drugs.Biomaterials · 2014Article
- Combinatorial peptide libraries: mining for cell-binding peptides.Chemical reviews · 2014Review
- Basics and recent advances in peptide and protein drug delivery.Therapeutic delivery · 2013Article
- An independent endocytic pathway stimulates different monocyte subsets by the a2 N-terminus domain of vacuolar-ATPase.Oncoimmunology · 2013Article
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ligand-directed delivery of agents to leukemia and lymphoma cells has the potential to yield new mechanistic disease insights and targeted therapies. Here we set out to target the macropinocytotic pathway with a combinatorial approach. From the screening of acute T-lymphoblastic leukemia Molt-4 cells with a random phage-display peptide library, we isolated a phage displaying the sequence CAYHRLRRC. This peptide contains a lymph node-homing motif (Cys-Ala-Tyr) and a cell-penetrating motif (Arg-Leu-Arg-Arg). Binding of this ligand-directed phage to a large panel of leukemia/lymphoma cells and to patient-derived samples was much higher than to non-leukemia control cells. CAYHRLRRC phage internalization into Molt-4 cells is both energy- and temperature-dependent. Flow cytometry with fluorescein-labeled peptide and endocytosis blocking with specific inhibitors revealed that CAYHRLRRC is indeed taken up through macropinocytosis in Molt-4 and K562 human leukemia cells. Unexpectedly, the cell surface receptor for the CAYHRLRRC peptide is not a heparan sulfate proteoglycan as it would be predicted for other cell-penetrating peptides. Confirming this interpretation, a CAYHRLRRC-directed peptidomimetic-induced cell death in all the leukemia and lymphoma cells was evaluated, whereas a control transactivator of transcription protein (tat)-directed proapoptotic peptidomimetic was non-selective. In summary, the targeting peptide CAYHRLRRC is selectively internalized through macropinocytosis in leukemia and lymphoma cells and has potential as a drug lead for ligand-directed anti-leukemia therapies.
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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.