The enamel matrix derivative (Emdogain® ) enhances human tongue carcinoma cells gelatinase production, migration and metastasis formation

• Published in: Oral oncology 2008-08, Vol.44 (8), p.733-742
• Main Authors: Laaksonen, Matti, Suojanen, Juho, Nurmenniemi, Sini, Läärä, Esa, Sorsa, Timo, Salo, Tuula
• Format: Article
• Language: English
• Subjects: Amelogenin - pharmacology; Animals; Apoptosis - drug effects; Biological and medical sciences; Carcinoma, Squamous Cell - enzymology; Carcinoma, Squamous Cell - secondary; Cell Movement - drug effects; Cell Proliferation - drug effects; Dental Enamel Proteins - adverse effects; Emdogain; Enzyme Induction; Enzyme-Linked Immunosorbent Assay; Female; Hematology, Oncology and Palliative Medicine; Humans; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase Inhibitors; Medical sciences; Metastasis; Mice; Migration; Otolaryngology; Otorhinolaryngology. Stomatology; Tongue carcinoma; Tongue Neoplasms - enzymology; Tongue Neoplasms - pathology; Tumor Cells, Cultured; Tumors; Wound Healing - drug effects
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2007.09.008

Summary Enamel matrix derivative Emdogain® (EMD) is widely used in periodontal treatment to regenerate lost connective tissue and to improve the attachment of the teeth. Gelatinases (MMP-2 and -9) have an essential role in the promotion and progression of oral cancer growth and metastasis formation. We studied the effects of EMD on human tongue squamous cell carcinoma (HSC-3) cells in vitro and in vivo. In vitro, EMD (100 μg/ml and 200 μg/ml) remarkably induced the MMP-2 and -9 production from HSC-3 cells analysed by zymography and enzyme-linked immunosorbent assay. EMD also slightly induced the MMP-2 and -9 production from benign human mucosal keratinocytes (HMK). Furthermore, EMD clearly induced the transmigration of HSC-3 cells but had no effect on the HMK migration in transwell assays. The in vitro wound closure of HSC-3 cells was notably accelerated by EMD, whereas it had only minor effect on the wound closure of HMKs. The migration of both cell lines was inhibited by a selective cyclic anti-gelatinolytic peptide CTT-2. EMD had no effect on HSC-3 cell proliferation or apoptosis and only a limited effect on cell attachment to various extracellular matrix components. The in vivo mice experiment revealed that EMD substantially induced HSC-3 xenograft metastasis formation. Our results suggest that the use of EMD for patients with oral mucosal carcinomas or premalignant lesions should be carefully considered, possibly avoided.