Heparin-binding epidermal growth factor-like growth factor is a potent regulator of invasion activity in oral squamous cell carcinoma

Ohnishi,Yuichi; Inoue,Hiroshi; Furukawa,Masayuki; Kakudo,Kenji; Nozaki,Masami

doi:10.3892/or.2011.1616

Heparin-binding epidermal growth factor-like growth factor is a potent regulator of invasion activity in oral squamous cell carcinoma

Authors:
- Yuichi Ohnishi
- Hiroshi Inoue
- Masayuki Furukawa
- Kenji Kakudo
- Masami Nozaki
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Affiliations: Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, Chuo-ku, Osaka 540-0008, Japan, Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Published online on: December 30, 2011 https://doi.org/10.3892/or.2011.1616
Pages: 954-958

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Abstract

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) has been shown to stimulate the growth of various cell types in an autocrine or paracrine manner. Although HB-EGF is widely expressed in tumors when compared with normal tissue, its contribution to cancer progression remains obscure. The objective of this study was to explore the effects of HB-EGF on proliferation, invasion activity and MMP-9 levels of an oral squamous cell carcinoma cell line, HSC3, in vitro. MTT assays, Matrigel invasion assays and RT-PCR in combination with RNA interference (RNAi) were used in this study. An RNAi-mediated decrease in HB-EGF expression reduced invasion activity and MMP-9 mRNA levels, but not proliferation, in HSC3 cells. The addition of purified HB-EGF to cell culture medium upregulated MMP-9 mRNA levels in HSC3 cells. Furthermore, the TACE inhibitor TAPI-2 or EGFR inhibitor AG1478 decreased MMP-9 mRNA levels in HSC3 cells. These data indicate that HB-EGF released from HSC3 cells by TACE stimulates EGFR in an autocrine manner, which in turn activates invasion activity via MMP-9 upregulation.

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