Antitumor Effects of CRM197, A Specific Inhibitor of HB-EGF, in T-Cell Acute Lymphoblastic Leukemia
The therapeutic outcome for T-cell acute lymphoblastic leukemia (T-ALL) remains poor; thus, novel, targeted therapies are urgently needed. Recently, we showed that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family, is a promising target for the treatment...
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| Veröffentlicht in: | Anticancer research 2011-07, Vol.31 (7), p.2483-2488 |
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| creator | KUNAMI, Naoko YOTSUMOTO, Fusanori ISHITSUKA, Kenji FUKAMI, Tatsuya ODAWARA, Takashi MANABE, Sadao ISHIKAWA, Toyokazu TAMURA, Kazuo KUROKI, Masahide MIYAMOTO, Shingo |
| description | The therapeutic outcome for T-cell acute lymphoblastic leukemia (T-ALL) remains poor; thus, novel, targeted therapies are urgently needed. Recently, we showed that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family, is a promising target for the treatment of various types of cancer. The aim of the present study was to investigate whether HB-EGF is a therapeutic target for T-ALL, and to further elucidate the antitumor effects of a specific inhibitor of HB-EGF, cross-reacting material 197 (CRM197). We elucidated the expression of HB-EGF in T-ALL cell lines, and evaluated the effect of CRM197 on these cells alone or in combination with anticancer agent. The expression of EGFR and EGFR ligands was determined by flow cytometry, RT-PCR and real-time quantitative PCR. Induction of apoptosis was assessed by TUNEL assay. HB-EGF was strongly expressed by T-ALL cell lines, and the expression of both HB-EGF and EGFR was enhanced by doxorubicin. CRM197 induced apoptosis, and furthermore, the combination of CRM197 plus doxorubicin enhanced cytotoxicity in a T-ALL cell line. These results suggest that HB-EGF is a promising therapeutic target for T-ALL. |
| format | Article |
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Recently, we showed that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family, is a promising target for the treatment of various types of cancer. The aim of the present study was to investigate whether HB-EGF is a therapeutic target for T-ALL, and to further elucidate the antitumor effects of a specific inhibitor of HB-EGF, cross-reacting material 197 (CRM197). We elucidated the expression of HB-EGF in T-ALL cell lines, and evaluated the effect of CRM197 on these cells alone or in combination with anticancer agent. The expression of EGFR and EGFR ligands was determined by flow cytometry, RT-PCR and real-time quantitative PCR. Induction of apoptosis was assessed by TUNEL assay. HB-EGF was strongly expressed by T-ALL cell lines, and the expression of both HB-EGF and EGFR was enhanced by doxorubicin. CRM197 induced apoptosis, and furthermore, the combination of CRM197 plus doxorubicin enhanced cytotoxicity in a T-ALL cell line. These results suggest that HB-EGF is a promising therapeutic target for T-ALL.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 21873163</identifier><language>eng</language><publisher>Attiki: International Institute of Anticancer Research</publisher><subject><![CDATA[Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents, Phytogenic - administration & dosage ; Antineoplastic Agents, Phytogenic - pharmacology ; Apoptosis - drug effects ; Bacterial Proteins - administration & dosage ; Bacterial Proteins - pharmacology ; Biological and medical sciences ; Breast Neoplasms - pathology ; Cell Line, Tumor - drug effects ; Cell Line, Tumor - metabolism ; Diphtheria Toxin - administration & dosage ; Diphtheria Toxin - pharmacology ; Doxorubicin - administration & dosage ; Doxorubicin - pharmacology ; Drug Screening Assays, Antitumor ; Drug Synergism ; Gene Expression Regulation, Neoplastic - drug effects ; Genes, erbB-1 ; Growth Inhibitors - administration & dosage ; Growth Inhibitors - pharmacology ; Hematologic and hematopoietic diseases ; Heparin-binding EGF-like Growth Factor ; Humans ; Intercellular Signaling Peptides and Proteins - biosynthesis ; Jurkat Cells - drug effects ; Jurkat Cells - metabolism ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Ligands ; Medical sciences ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Protein Kinase Inhibitors - administration & dosage ; Protein Kinase Inhibitors - pharmacology ; Receptor, Epidermal Growth Factor - biosynthesis ; Signal Transduction - drug effects ; Tumors]]></subject><ispartof>Anticancer research, 2011-07, Vol.31 (7), p.2483-2488</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>309,310,314,776,780,785,786,23909,23910,25118</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24458902$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21873163$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KUNAMI, Naoko</creatorcontrib><creatorcontrib>YOTSUMOTO, Fusanori</creatorcontrib><creatorcontrib>ISHITSUKA, Kenji</creatorcontrib><creatorcontrib>FUKAMI, Tatsuya</creatorcontrib><creatorcontrib>ODAWARA, Takashi</creatorcontrib><creatorcontrib>MANABE, Sadao</creatorcontrib><creatorcontrib>ISHIKAWA, Toyokazu</creatorcontrib><creatorcontrib>TAMURA, Kazuo</creatorcontrib><creatorcontrib>KUROKI, Masahide</creatorcontrib><creatorcontrib>MIYAMOTO, Shingo</creatorcontrib><title>Antitumor Effects of CRM197, A Specific Inhibitor of HB-EGF, in T-Cell Acute Lymphoblastic Leukemia</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>The therapeutic outcome for T-cell acute lymphoblastic leukemia (T-ALL) remains poor; thus, novel, targeted therapies are urgently needed. Recently, we showed that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family, is a promising target for the treatment of various types of cancer. The aim of the present study was to investigate whether HB-EGF is a therapeutic target for T-ALL, and to further elucidate the antitumor effects of a specific inhibitor of HB-EGF, cross-reacting material 197 (CRM197). We elucidated the expression of HB-EGF in T-ALL cell lines, and evaluated the effect of CRM197 on these cells alone or in combination with anticancer agent. The expression of EGFR and EGFR ligands was determined by flow cytometry, RT-PCR and real-time quantitative PCR. Induction of apoptosis was assessed by TUNEL assay. HB-EGF was strongly expressed by T-ALL cell lines, and the expression of both HB-EGF and EGFR was enhanced by doxorubicin. CRM197 induced apoptosis, and furthermore, the combination of CRM197 plus doxorubicin enhanced cytotoxicity in a T-ALL cell line. These results suggest that HB-EGF is a promising therapeutic target for T-ALL.</description><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents, Phytogenic - administration & dosage</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Bacterial Proteins - administration & dosage</subject><subject>Bacterial Proteins - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor - drug effects</subject><subject>Cell Line, Tumor - metabolism</subject><subject>Diphtheria Toxin - administration & dosage</subject><subject>Diphtheria Toxin - pharmacology</subject><subject>Doxorubicin - administration & dosage</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Drug Synergism</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Genes, erbB-1</subject><subject>Growth Inhibitors - administration & dosage</subject><subject>Growth Inhibitors - pharmacology</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Heparin-binding EGF-like Growth Factor</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - biosynthesis</subject><subject>Jurkat Cells - drug effects</subject><subject>Jurkat Cells - metabolism</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><subject>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Protein Kinase Inhibitors - administration & dosage</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Receptor, Epidermal Growth Factor - biosynthesis</subject><subject>Signal Transduction - drug effects</subject><subject>Tumors</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0MtKxDAUBuAiijOOvoJkI26mkEtzW9ZhblARdFyXJE2YaG826WLe3oIjLl2dxf-dw8-5SOaIS5RySuBlMoeYwpRDSGfJTQgfEDImBblOZhgJThAj88TkbfRxbLoBrJ2zJgbQObB6fUaSL0EO3nprvPMG7Nuj1z5Obsp3T-l6u1kC34JDurJ1DXIzRguKU9MfO12rEKeVwo6ftvHqNrlyqg727jwXyftmfVjt0uJlu1_lRdpjjmOKOHaOwUxJzbC1SLFKEJJlWjsiCZZcaqqlxA5BhlmlKcNUZKbCiJMKQUEWyePP3X7ovkYbYtn4YKZ2qrXdGEoJOeIwE-xfKQSVUMqMTvL-LEfd2KrsB9-o4VT-fnACD2egglG1G1RrfPhzWUaFhJh8A_pMdqU</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>KUNAMI, Naoko</creator><creator>YOTSUMOTO, Fusanori</creator><creator>ISHITSUKA, Kenji</creator><creator>FUKAMI, Tatsuya</creator><creator>ODAWARA, Takashi</creator><creator>MANABE, Sadao</creator><creator>ISHIKAWA, Toyokazu</creator><creator>TAMURA, Kazuo</creator><creator>KUROKI, Masahide</creator><creator>MIYAMOTO, Shingo</creator><general>International Institute of Anticancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20110701</creationdate><title>Antitumor Effects of CRM197, A Specific Inhibitor of HB-EGF, in T-Cell Acute Lymphoblastic Leukemia</title><author>KUNAMI, Naoko ; YOTSUMOTO, Fusanori ; ISHITSUKA, Kenji ; FUKAMI, Tatsuya ; ODAWARA, Takashi ; MANABE, Sadao ; ISHIKAWA, Toyokazu ; TAMURA, Kazuo ; KUROKI, Masahide ; MIYAMOTO, Shingo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p272t-172ff604a9b62ee1a6d83344bbf3932979b5b992f10626db562584cd2173d1083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents, Phytogenic - administration & dosage</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Bacterial Proteins - administration & dosage</topic><topic>Bacterial Proteins - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Line, Tumor - drug effects</topic><topic>Cell Line, Tumor - metabolism</topic><topic>Diphtheria Toxin - administration & dosage</topic><topic>Diphtheria Toxin - pharmacology</topic><topic>Doxorubicin - administration & dosage</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Drug Synergism</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Genes, erbB-1</topic><topic>Growth Inhibitors - administration & dosage</topic><topic>Growth Inhibitors - pharmacology</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Heparin-binding EGF-like Growth Factor</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - biosynthesis</topic><topic>Jurkat Cells - drug effects</topic><topic>Jurkat Cells - metabolism</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. 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Recently, we showed that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family, is a promising target for the treatment of various types of cancer. The aim of the present study was to investigate whether HB-EGF is a therapeutic target for T-ALL, and to further elucidate the antitumor effects of a specific inhibitor of HB-EGF, cross-reacting material 197 (CRM197). We elucidated the expression of HB-EGF in T-ALL cell lines, and evaluated the effect of CRM197 on these cells alone or in combination with anticancer agent. The expression of EGFR and EGFR ligands was determined by flow cytometry, RT-PCR and real-time quantitative PCR. Induction of apoptosis was assessed by TUNEL assay. HB-EGF was strongly expressed by T-ALL cell lines, and the expression of both HB-EGF and EGFR was enhanced by doxorubicin. CRM197 induced apoptosis, and furthermore, the combination of CRM197 plus doxorubicin enhanced cytotoxicity in a T-ALL cell line. These results suggest that HB-EGF is a promising therapeutic target for T-ALL.</abstract><cop>Attiki</cop><pub>International Institute of Anticancer Research</pub><pmid>21873163</pmid><tpages>6</tpages></addata></record> |
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| subjects | Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Antineoplastic Agents, Phytogenic - administration & dosage Antineoplastic Agents, Phytogenic - pharmacology Apoptosis - drug effects Bacterial Proteins - administration & dosage Bacterial Proteins - pharmacology Biological and medical sciences Breast Neoplasms - pathology Cell Line, Tumor - drug effects Cell Line, Tumor - metabolism Diphtheria Toxin - administration & dosage Diphtheria Toxin - pharmacology Doxorubicin - administration & dosage Doxorubicin - pharmacology Drug Screening Assays, Antitumor Drug Synergism Gene Expression Regulation, Neoplastic - drug effects Genes, erbB-1 Growth Inhibitors - administration & dosage Growth Inhibitors - pharmacology Hematologic and hematopoietic diseases Heparin-binding EGF-like Growth Factor Humans Intercellular Signaling Peptides and Proteins - biosynthesis Jurkat Cells - drug effects Jurkat Cells - metabolism Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Ligands Medical sciences Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - metabolism Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology Protein Kinase Inhibitors - administration & dosage Protein Kinase Inhibitors - pharmacology Receptor, Epidermal Growth Factor - biosynthesis Signal Transduction - drug effects Tumors |
| title | Antitumor Effects of CRM197, A Specific Inhibitor of HB-EGF, in T-Cell Acute Lymphoblastic Leukemia |
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