Abstract
In previous research, we found α-enolase to be inversely correlated with progression-free and overall survival in lung cancer patients and detected α-enolase on the surface of lung cancer cells. Based on these findings, we hypothesized that surface α-enolase has a significant role in cancer metastasis and tested this hypothesis in the current study. We found that α-enolase was co-immunoprecipitated with urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen in lung cancer cells and interacted with these proteins in a cell-free dot blotting assay, which can be interrupted by α-enolase-specific antibody. α-Enolase in lung cancer cells co-localized with these proteins and was present at the site of pericellular degradation of extracellular matrix components. Treatment with antibody against α-enolase in vitro suppressed cell-associated plasminogen and matrix metalloproteinase activation, collagen and gelatin degradation, and cell invasion. Examination of the effect of treatment with shRNA plasmids revealed that down regulation of α-enolase decreases extracellular matrix degradation by and the invasion capacity of lung cancer cells. Adoptive transfer of α-enolase-specific antibody to mice resulted in accumulation of antibody in subcutaneous tumor and inhibited the formation of tumor metastasis in lung and bone. This study demonstrated that surface α-enolase promotes extracellular matrix degradation and invasion of cancer cells and that targeting surface α-enolase is a promising approach to suppress tumor metastasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / pharmacology
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Biomarkers, Tumor / antagonists & inhibitors
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Biomarkers, Tumor / metabolism
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Bone Neoplasms / drug therapy
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Bone Neoplasms / secondary
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Cell Line, Tumor
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Cell Membrane / metabolism*
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Cell Movement
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism
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Extracellular Matrix / metabolism*
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Humans
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Immunocompromised Host
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Lung Neoplasms / metabolism
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Lung Neoplasms / mortality
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Lung Neoplasms / pathology
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Male
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Mice
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Neoplasm Metastasis
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Neoplasms / metabolism*
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Neoplasms / mortality
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Neoplasms / pathology*
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Phosphopyruvate Hydratase / antagonists & inhibitors
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Phosphopyruvate Hydratase / metabolism*
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Plasminogen / metabolism
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Protein Binding
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Receptors, Urokinase Plasminogen Activator / metabolism
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Tumor Suppressor Proteins / antagonists & inhibitors
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Tumor Suppressor Proteins / metabolism
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Urokinase-Type Plasminogen Activator / metabolism
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Xenograft Model Antitumor Assays
Substances
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Antibodies, Monoclonal
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Biomarkers, Tumor
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DNA-Binding Proteins
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Receptors, Urokinase Plasminogen Activator
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Tumor Suppressor Proteins
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Plasminogen
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Urokinase-Type Plasminogen Activator
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ENO1 protein, human
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Phosphopyruvate Hydratase
Grants and funding
This work was supported by grants from the Department of Health, Taiwan, to G.-C. Chang (China Medical University Hospital Cancer Research Center of Excellence, DOH100-TD-C-111-005), N.-Y. Shih (DOH99-TD-G-111-009), and C.-C. Kuo (DOH100-TD-C-111-004) and grants from the National Science Council, Taiwan, to K.-J. Liu (NSC98-3112-B-400-012, 99-3112-B-400-004, and 100-3112-B-400-014), and C.-C. Kuo (NSC98-2320-B-400-003-MY3). G.-C. Chang was supported by a VGHTC grant (TCVGH-963205C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.