ArticleBMC cell biology2010
Monoclonal antibody 4C5 prevents activation of MMP2 and MMP9 by disrupting their interaction with extracellular HSP90 and inhibits formation of metastatic breast cancer cell deposits.
Article in BMC cell biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 133 citations in OpenAlex.
- Hypoxia-ROS-HSP Triad Axis in Cancer: Mechanisms, Crosstalk, and Therapeutic Implications.Cells · 2026Review
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- HSP90α and KLK6 Co-Regulate Stress-Induced Prostate Cancer Cell Motility.bioRxiv : the preprint server for biology · 2025Article
- siRNA-mediated inhibition of NTT-MMP-2 reduces oxidative stress and apoptotic signaling in an ex vivo model of ischemia/reperfusion injury.Scientific reports · 2025Article
- Determination of vaginal cytology and MMP-9 expression during early pregnancy in mice.Veterinary and animal science · 2024Article
- The Role of eHsp90 in Extracellular Matrix Remodeling, Tumor Invasiveness, and Metastasis.Cancers · 2024Review
- Extracellular heat shock protein 90 alpha (eHsp90α)'s role in cancer progression and the development of therapeutic strategies.European journal of medicinal chemistry · 2024Review
- Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells.Cell death & disease · 2023Article
- Extracellular Hsp90 Binds to and Aligns Collagen-1 to Enhance Breast Cancer Cell Invasiveness.Cancers · 2023Article
- The Continuing Saga of Tissue Inhibitor of Metalloproteinase 2: Emerging Roles in Tissue Homeostasis and Cancer Progression.The American journal of pathology · 2023Review
- Synthesis and Validation of the First Cell-Impermeable Hsp90α-Selective Inhibitors.ACS medicinal chemistry letters · 2023Article
- Methods to Assess the Impact of Hsp90 Chaperone Function on Extracellular Client MMP2 Activity.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- Hsp90: From Cellular to Organismal Proteostasis.Cells · 2022Review
- Extracellular Heat Shock Protein-90 (eHsp90): Everything You Need to Know.Biomolecules · 2022Review
- Secreted HSP90α-LRP1 Signaling Promotes Tumor Metastasis and Chemoresistance in Pancreatic Cancer.International journal of molecular sciences · 2022Article
- Targeting extracellular Hsp90: A unique frontier against cancer.Frontiers in molecular biosciences · 2022Review
- Proliferation, Metastasis, and Radiosensitivity of Nasopharyngeal Carcinoma Cells in the Expression and Effect of Kiwifruit Extract through the Regulation of miR-205-5p.Journal of oncology · 2022Article
- Extracellular Hsp90α Supports the ePKM2-GRP78-AKT Axis to Promote Tumor Metastasis.Frontiers in oncology · 2022Article
- Tetrandrine Inhibits Epithelial-Mesenchymal Transition in IL-6-Induced HCT116 Human Colorectal Cancer Cells.OncoTargets and therapy · 2021Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHeat shock protein 90 (HSP90) is a molecular chaperone that is considered a new target for the treatment of cancer. Increasing data reveal an extracellular chaperoning activity for HSP90. Here we investigate the interaction of the secreted isoforms of HSP90 with matrix metalloproteinases (MMP) MMP2 and MMP9. Moreover we examine the role of a monoclonal antibody (mAb) against HSP90, mAb 4C5, regarding these interactions and its value as a potential inhibitor of human breast cancer cell invasion and metastasis.
resultsOur results showed that both HSP90alpha and HSP90beta are secreted by MDAMB453 human breast cancer cells and interact with MMP2 and MMP9. MAb 4C5, while not affecting the secretion of inactive MMPs, inhibits their activation by disrupting their interaction extracellularly with both isoforms of HSP90. The in vivo studies revealed that mAb 4C5 significantly inhibits the metastatic deposit formation of MDAMB453 cells into the lungs of SCID mice.
conclusionBoth isoforms of HSP90 are secreted by MDAMB453 cells and interact with MMP2 and MMP9. MAb 4C5 prevents MMP2 and MMP9 activation, by disrupting their interaction with HSP90. Finally mAb 4C5 significantly inhibits the metastatic deposit formation of MDAMB453 cells, by preventing their extravasation and infiltration in the lung tissue and therefore it could be used as a potential therapeutic agent for cancer metastasis.
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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.