Document Detail


Alteration of MMP-2 and -14 expression by imatinib in HPV-positive and -negative squamous cell carcinoma.
MedLine Citation:
PMID:  22576800     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Anne Faber; Alexander Sauter; Sarah Hoedt; Karl Hoermann; Philipp Erben; Ralf-Dieter Hofheinz; Ulrich Sommer; Jens Stern-Straeter; David Johannes Schultz
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-20
Journal Detail:
Title:  Oncology reports     Volume:  28     ISSN:  1791-2431     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-5-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  -    
Other Details:
Languages:  ENG     Pagination:  172-178     Citation Subset:  -    
Affiliation:
Department of Otorhinolaryngology Head and Neck Surgery, University Medical Centre Mannheim, D-68167 Mannheim, Germany.
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