title: Heparin-binding EGF-like growth factor enhances the activity of invasion and metastasis in thyroid cancer cells.
abstract: Thyroid cancer sometimes contains poorly differentiated components, which have the potential of invasion and metastasis. We evaluated the possible roles of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, in cell growth and invasion of thyroid cancer cells, and demonstrated that HB-EGF is not only a potent mitogen but also a chemotactic factor in the thyroid cancer cells 8305C and SW579. The HB-EGF-mediated chemotaxis was inhibited by neutralizing antibody against the EGF receptor (EGFR/HER1/ErbB1) or tyrphostin AG1478, a specific inhibitor of the EGFR tyrosine kinase. The HB-EGF mRNA and protein expression was also analyzed using RT-PCR and immunofluorescence methods, respectively. In addition, in clinical immunohistochemical study, increased expression of HB-EGF and its receptors, HER1 and EGFR4 (HER4/ErbB4), was observed in thyroid carcinoma cells. Our findings suggest that HB-EGF acts as a potent paracrine and/or autocrine chemotactic factor as well as a mitogen that mediates HER1 and/or HER4 in the invasion and metastasis of thyroid carcinoma cells, including poorly differentiated papillary carcinomas or undifferentiated/anaplastic carcinomas. These data may aid in the development of novel therapeutic strategies for thyroid cancer.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara, Japan. iota@naramed-u.ac.jp
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ota
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Masui
authors.forename: Katsunari
authors.initials: K
authors.lastname: Yane
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoi
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002633:Chemotaxis / Q000187:drug effects; D004167:Diphtheria Toxin / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D066247:Receptor, ErbB-4; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D057134:Antibodies, Neutralizing; D004167:Diphtheria Toxin; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011799:Quinazolines; D012333:RNA, Messenger; D020032:Tyrphostins; C101044:RTKI cpd; C512478:EGFR protein, human; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4
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