Heparin-binding EGF-like growth factor enhances the activity of invasion and metastasis in thyroid cancer cells

Ota,Ichiro; Higashiyama,Shigeki; Masui,Takashi; Yane,Katsunari; Hosoi,Hiroshi; Matsuura,Nariaki

doi:10.3892/or.2013.2659

Heparin-binding EGF-like growth factor enhances the activity of invasion and metastasis in thyroid cancer cells

Authors:
- Ichiro Ota
- Shigeki Higashiyama
- Takashi Masui
- Katsunari Yane
- Hiroshi Hosoi
- Nariaki Matsuura
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Affiliations: Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara, Japan, Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan, Department of Otolaryngology, Kinki University Nara Hospital, Ikoma, Nara, Japan, Department of Molecular Pathology, School of Allied Health Science, Osaka University Faculty of Medicine, Suita, Osaka, Japan
Published online on: August 6, 2013 https://doi.org/10.3892/or.2013.2659
Pages: 1593-1600
Copyright: © Ota et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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