Heparin-binding epidermal growth factor-like growth factor is a potent             regulator of invasion activity in oral squamous cell carcinoma.
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.
Second Department of Oral and Maxillofacial Surgery, Osaka Dental                     University, Chuo-ku, Osaka 540-0008, Japan.
Yuichi
Y
Ohnishi
Hiroshi
H
Inoue
Masayuki
M
Furukawa
Kenji
K
Kakudo
Masami
M
Nozaki
D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072198:ADAM17 Protein; D019898:Autocrine Communication; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011480:Protease Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020032:Tyrphostins / Q000494:pharmacology
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D006877:Hydroxamic Acids; D036341:Intercellular Signaling Peptides and Proteins; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012333:RNA, Messenger; C099410:TAPI-2; D020032:Tyrphostins; C101044:RTKI cpd; C512478:EGFR protein, human; D066246:ErbB Receptors; D051722:ADAM Proteins; D020780:Matrix Metalloproteinase 9; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human