ArticleThe Journal of biological chemistry2014
A novel CD44-binding peptide from the pro-matrix metalloproteinase-9 hemopexin domain impairs adhesion and migration of chronic lymphocytic leukemia (CLL) cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Digging into the Solubility Factor in Cancer Diagnosis: A Case of Soluble CD44 Protein.Biosensors · 2025Review
- Tumor Cell Survival Factors and Angiogenesis in Chronic Lymphocytic Leukemia: How Hot Is the Link?Cancers · 2024Review
- Article
- Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata.Scientific reports · 2021Article
- Simultaneous targeting of CD44 and MMP9 catalytic and hemopexin domains as a therapeutic strategy.The Biochemical journal · 2021Article
- Cell-specific expression of the transcriptional regulator RHAMM provides a timing mechanism that controls appropriate wound re-epithelialization.The Journal of biological chemistry · 2020Article
- Design and Biological Evaluation of Colchicine-CD44-Targeted Peptide Conjugate in an In Vitro Model of Crystal Induced Inflammation.Molecules (Basel, Switzerland) · 2019Article
- Characterizing CD44 regulatory microRNAs as putative therapeutic agents in human melanoma.Oncotarget · 2019Article
- MicroRNA-144 targets APP to regulate AML1/ETOOncology letters · 2019Article
- Molecular Players in Hematologic Tumor Cell Trafficking.Frontiers in immunology · 2019Review
- The biology and role of CD44 in cancer progression: therapeutic implications.Journal of hematology & oncology · 2018Review
- Microenvironment-induced CD44v6 promotes early disease progression in chronic lymphocytic leukemia.Blood · 2018Article
- CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression.Frontiers in cell and developmental biology · 2018Review
- Functional peptides for cartilage repair and regeneration.American journal of translational research · 2018Article
- Targeting the Hemopexin-like Domain of Latent Matrix Metalloproteinase-9 (proMMP-9) with a Small Molecule Inhibitor Prevents the Formation of Focal Adhesion Junctions.ACS chemical biology · 2017Article
- Inhibition of MMP-9-dependent Degradation of Gelatin, but Not Other MMP-9 Substrates, by the MMP-9 Hemopexin Domain Blades 1 and 4.The Journal of biological chemistry · 2016Article
- Hyaluronan as a therapeutic target in human diseases.Advanced drug delivery reviews · 2016Review
- Matricryptins Network with Matricellular Receptors at the Surface of Endothelial and Tumor Cells.Frontiers in pharmacology · 2016Review
- Evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer.Clinical immunology (Orlando, Fla.) · 2015Review
- Concise Review: Emerging Role of CD44 in Cancer Stem Cells: A Promising Biomarker and Therapeutic Target.Stem cells translational medicine · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
(pro)MMP-9 binds to CLL cells through the PEX9 domain and contributes to CLL progression. To biochemically characterize this interaction and identify potential therapeutic targets, we prepared GST-PEX9 forms containing structural blades B1B2 or B3B4. We recently described a sequence in blade B4 (P3 sequence) that bound α4β1 integrin and partially impaired cell adhesion and migration. We have now studied the possible contribution of the B1B2 region to cell interaction with PEX9. CLL cells bound to GST-B1B2 and CD44 was the primary receptor. GST-B1B2 inhibited CLL cell migration as effectively as GST-B3B4. Overlapping synthetic peptides spanning the B1B2 region identified the sequence FDAIAEIGNQLYLFKDGKYW, present in B1 and contained in peptide P6, as the most effective site. P6 inhibited cell adhesion to PEX9 in a dose-dependent manner and with an IC50 value of 90 μM. P6 also inhibited cell adhesion to hyaluronan but had no effect on adhesion to VCAM-1 (α4β1 integrin ligand), confirming its specific interaction with CD44. Spatial localization analyses mapped P6 to the central cavity of PEX9, in close proximity to the previously identified P3 sequence. Both P6 and P3 equally impaired cell adhesion to (pro)MMP-9. Moreover, P6 synergistically cooperated with P3, resulting in complete inhibition of CLL cell binding to PEX9, chemotaxis, and transendothelial migration. Thus, P6 is a novel sequence in PEX9 involved in cell-PEX9/(pro)MMP-9 binding by interacting with CD44. Targeting both sites, P6 and P3, should efficiently prevent (pro)MMP-9 binding to CLL cells and its pathological consequences.
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