tapi-2 and Carcinoma--Squamous-Cell

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.

Topics: ADAM Proteins; ADAM17 Protein; Autocrine Communication; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; ErbB Receptors; Heparin-binding EGF-like Growth Factor; Humans; Hydroxamic Acids; Intercellular Signaling Peptides and Proteins; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Protease Inhibitors; Protein Kinase Inhibitors; Quinazolines; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Messenger; Signal Transduction; Time Factors; Tongue Neoplasms; Tyrphostins