Epidermal growth factor-like ligands differentially up-regulate matrix metalloproteinase 9 in head and neck squamous carcinoma cells.

摘要: Head and neck squamous cell carcinomas (HNSCCs) are characterized by a marked propensity for local invasion dissemination to cervical lymph nodes, with distant metastases developing in 30–40% of cases. Overexpression the epidermal growth factor receptor (EGFR/c- erb B-1) and/or its ligands high levels certain matrix metalloproteinases (MMPs) have been associated poor prognosis. The aim this study was examine effects EGFR on gelatinase expression HNSCC lines. We tested (EGF), transforming α, betacellulin, heparin-binding EGF, amphiregulin measured gelatinases MMP-9 MMP-2 an established carcinoma line (Detroit-562) two lines newly derived from patients head cancers (SIHN-005A SIHN-006). Incubation EGF-like up-regulated (but not MMP-2) as semiquantitative reverse transcription-PCR dose-dependent manner, being most cells undetectable low levels. Maximum stimulation obtained concentration range 10–100 nm. In addition, we confirmed zymography that gelatinolytic activity consistent ( M r 92,000) parallel increases gene expression. Betacellulin (which binds both c- B-4 receptors) consistently increased activation significantly greater degree than other four when at equimolar concentrations. up-regulation, all tumor through Matrigel vitro Transwell assays. These activities were independent ligand proliferation. Antagonist (ICR62) or agonist (ICR9) anti-EGFR monoclonal antibodies, respectively, inhibited potentiated induced ligands. Furthermore, antibody neutralizes (Ab1) also ligand-induced HNSCC. used these studies (and larger series reported here) generally expressed multiple B receptors results indicate autocrine paracrine signaling potentiates invasive potential via selective up-regulation MMP-9. such betacellulin is commonly HNSCC), which can bind activate receptors, may be especially potent regard.