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

机译:肝素结合型EGF样生长因子增强甲状腺癌细胞的侵袭和转移活性

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摘要

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.
机译:甲状腺癌有时包含分化差的成分,可能具有侵袭和转移的潜力。我们评估了表皮生长因子(EGF)家族成员肝素结合型EGF样生长因子(HB-EGF)在甲状腺癌细胞的细胞生长和侵袭中的可能作用,并证明了HB-EGF并非如此在甲状腺癌细胞8305C和SW579中,它不仅是有效的促分裂原,而且是趋化因子。 HB-EGF介导的趋化性被中和抗EGF受体的抗体(EGFR / HER1 / ErbB1)或酪氨酸激酶AG1478(酪氨酸激酶的特异性抑制剂)抑制。还分别使用RT-PCR和免疫荧光方法分析了HB-EGF mRNA和蛋白表达。此外,在临床免疫组织化学研究中,在甲状腺癌细胞中观察到HB-EGF及其受体HER1和EGFR4(HER4 / ErbB4)的表达增加。我们的研究结果表明,HB-EGF在甲状腺癌细胞(包括低分化乳头状癌或未分化/间变性癌)的侵袭和转移中起着有效的旁分泌和/或自分泌趋化因子以及介导HER1和/或HER4的有丝分裂原的作用。 。这些数据可能有助于开发新型的甲状腺癌治疗策略。

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