Antitumor Effects of CRM197, A Specific Inhibitor of HB-EGF, in T-Cell Acute Lymphoblastic Leukemia

• Published in: Anticancer research Vol. 31; no. 7; pp. 2483 - 2488
• Main Authors: KUNAMI, Naoko, YOTSUMOTO, Fusanori, ISHITSUKA, Kenji, FUKAMI, Tatsuya, ODAWARA, Takashi, MANABE, Sadao, ISHIKAWA, Toyokazu, TAMURA, Kazuo, KUROKI, Masahide, MIYAMOTO, Shingo
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.07.2011
• 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; Antineoplastic agent; DNA topoisomerase (ATP-hydrolysing); Enzyme; HB-EGF; Enzyme inhibitor; Malignant hemopathy; CRM197; Topoisomerase II inhibitor; Doxorubicin; Isomerases; Cancerology; Heparin-binding epidermal growth factor-like growth factor; Lymphoproliferative syndrome; Anthracyclins; T-ALL; Cancer; T cell acute lymphoblastic leukemia
• ISSN: 0250-7005; 1791-7530

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.