Abstract
Chondrosarcoma is a malignant tumor that produces cartilage matrix. The most lethal aspect is its metastatic property. We demonstrated that amphiregulin (AR) is significantly upregulated in highly aggressive cells. AR silencing markedly suppressed cell migration. Exogenous AR markedly increased cell migration by transactivation of α6β1 integrin expression. A neutralizing α6β1 integrin antibody can abolish AR-induced cell motility. Knockdown of AR inhibits metastasis of cells to the lung in vivo. Furthermore, elevated AR expression is positively correlated with α6β1 integrin levels and higher grades in patients. These findings can potentially serve as biomarker and therapeutic approach for controlling chondrosarcoma metastasis.
Keywords:
amphiregulin; cell migration; chondrosarcoma; integrin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amphiregulin
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Animals
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Antibodies / pharmacology
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Antineoplastic Agents / pharmacology
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Bone Neoplasms / drug therapy
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Bone Neoplasms / enzymology*
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Bone Neoplasms / genetics
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Bone Neoplasms / pathology
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Cell Line, Tumor
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Cell Movement / drug effects*
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Chondrosarcoma / drug therapy
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Chondrosarcoma / enzymology*
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Chondrosarcoma / genetics
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Chondrosarcoma / secondary
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Dose-Response Relationship, Drug
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EGF Family of Proteins / genetics
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EGF Family of Proteins / metabolism*
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EGF Family of Proteins / pharmacology
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Gene Expression Regulation, Neoplastic
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Humans
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Integrin alpha6beta1 / antagonists & inhibitors
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Integrin alpha6beta1 / genetics
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Integrin alpha6beta1 / metabolism*
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Lung Neoplasms / enzymology
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Lung Neoplasms / prevention & control
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Lung Neoplasms / secondary
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MAP Kinase Kinase 1 / genetics
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MAP Kinase Kinase 1 / metabolism*
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Male
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Mice, Nude
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Neoplasm Grading
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Neoplasm Invasiveness
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Phosphorylation
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RNA Interference
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Signal Transduction
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Time Factors
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism*
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Transfection
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Xenograft Model Antitumor Assays
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raf Kinases / genetics
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raf Kinases / metabolism*
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ras Proteins / genetics
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ras Proteins / metabolism*
Substances
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AREG protein, human
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Amphiregulin
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Antibodies
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Antineoplastic Agents
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Biomarkers, Tumor
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EGF Family of Proteins
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Integrin alpha6beta1
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Transcription Factor AP-1
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raf Kinases
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Extracellular Signal-Regulated MAP Kinases
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MAP Kinase Kinase 1
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MAP2K1 protein, human
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ras Proteins