title: Alteration of MMP-2 and -14 expression by imatinib in HPV-positive and             -negative squamous cell carcinoma.
abstract: Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial             malignancy. It is known to be the most common neoplasm appearing in the upper             aerodigestive tract. The poor 5‑year survival rate has remained unchanged in the             last decades even though improved techniques in surgery, radiation and chemotherapy             have been established. In contrast to the overall decreasing incidence of head             and neck cancer in the US, the incidence of HPV-associated oropharyngeal cancer             is increasing, indicating the importance of viral etiology. Furthermore, growth             and invasion of HNSCC are strongly influenced by the extracellular matrix (ECM).             Matrix metalloproteinases (MMP) have been shown to play key roles in the remodeling             of the ECM. Imatinib (STI 571) was originally designed to inhibit the BCR-ABL             tyrosine kinase in chronic myeloid leukaemia. But it also has an inhibitory impact,             e.g., on the protein-tyrosine-kinase (PTK) receptor c-kit and on its PTK activity             in HNSCC. In this study, we incubated the HNSCC cell lines HNSCC 11A and 14C and             the p16-positive SCC line CERV196 with increasing concentrations of imatinib or             carboplatin. After an incubation time of up to 10 days, we evaluated MMP-2 and             -14 expression by ELISA techniques and immunohistochemistry. MMP-2 and -14 expression             was demonstrated in all incubated tumor cell lines. Especially incubation with             imatinib resulted in a significant decrease in MMP expression in incubated cell             lines. Our results indicate that the expression of MMP-2 and -14 is suppressed             in the presence of imatinib. Thus, imatinib may exert in part its inhibitory effect             on malignant cell growth via the blockage of the signal transduction of PTK receptors.             Further studies are warranted, especially keeping in mind the moderate toxicity             of imatinib.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, University Medical Centre Mannheim, D-68167 Mannheim, Germany. faberanne@gmx.de
authors.forename: Anne
authors.initials: A
authors.lastname: Faber
authors.forename: Alexander
authors.initials: A
authors.lastname: Sauter
authors.forename: Sarah
authors.initials: S
authors.lastname: Hoedt
authors.forename: Karl
authors.initials: K
authors.lastname: Hoermann
authors.forename: Philipp
authors.initials: P
authors.lastname: Erben
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hofheinz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sommer
authors.forename: Jens
authors.initials: J
authors.lastname: Stern-Straeter
authors.forename: David Johannes
authors.initials: DJ
authors.lastname: Schultz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D016190:Carboplatin / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000821:virology; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000821:virology; D052162:Human papillomavirus 16; D006801:Humans; D000068877:Imatinib Mesylate; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016190:Carboplatin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14