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.

Effect of thyroidectomy on circulating angiogenic cytokines in papillary thyroid carcinoma and benign goiter: Potential for new biomarkers?

“…20 HBEGF, a mitogen and a potent chemotactic factor, mediates the invasion and metastasis of PTC. 10 PLGF plays critical roles in the pathologic angiogenesis of PTC through regulating matrix metalloproteinases. 11 PDGF-BB, recognized as the most potent lymphangiogenic factor, can bind with high affinity to PDGF receptor-a to promote lymphatic metastases in PTC.…”

Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates

“…67,68 HBEGF may be a key gene linking uterine overdistention with preterm labor, inflammation, and myometrial tissue remodeling; HBEGF has been identified as up-regulated in stretch of the human bladder, 69 spontaneous labor at term, 70 cell migration and tissue remodeling, 71,72 and as a chemotactic factor in cancer cells. 73 Up-regulation of TGFBI also acts to inhibit cell adhesions, thereby increasing cell motility. 74 Additional evidence for tissue remodeling came from the identification by IPA of activated canonical pathways (HMGB1, calpain proteases) and transcription factors (hepatocyte growth factor) classically associated with cell migration.…”

Non-Thermal Atmospheric Pressure Plasma Inhibits Thyroid Papillary Cancer Cell Invasion via Cytoskeletal Modulation, Altered MMP-2/-9/uPA Activity

“…However, it can sometimes be aggressive, with extracapsular spread, strap muscle, recurrent laryngeal nerve, and tracheal invasion, as well as metastasis to lymph nodes. In rare cases, thyroid papillary cancer can metastasize to lung or bone [2] , [3] . The presence of local or distant metastases affects tumor recurrence, patient survival rates, and quality of life, thereby leading to poor prognoses [4] .…”