Matrix metalloproteinase-2 and -14 in p16-positive and -negative HNSCC after exposure To 5-FU and docetaxel In Vitro

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world. While the incidence of HNSCC associated with tobacco and alcohol abuse is falling, the incidence of HNSCC associated with human papilloma virus (HPV) is rising. Proliferation, cell migration and formation of metastases are dependent on interactions between the tumor cells, tumor stromal cells and the extracellular matrix (ECM). Degradation of the ECM is a crucial step in the process of local tumor infiltration and formation of locoregional and distant metastases. Matrix metalloproteinases (MMPs) are a family of enzymes that are able to degrade the ECM. Locally advanced HNSCC with cervical node metastases are treated with docetaxel in induction chemotherapy (ICT) combined with platinum-based chemotherapy and 5-fluorouracil (5-FU) as standard clinical anti-neoplastic regimens. This study evaluated the expression of MMP-14 and MMP-2 in HPV-positive (CERV196) and HPV-negative squamous cell carcinoma (HNSCC 11A and 14C) and the alteration of expression levels after exposure to either docetaxel or 5-FU.

Materials and methods: Tumor cells were exposed to 5-FU or docetaxel in concentrations of 1.0 and 5.0 μmol/ml. MMP-protein expression was evaluated by enzyme-linked immunosorbent assay (ELISA) after 2, 3, 5, 8 and 10 days of incubation.

Results: Docetaxel exposure significantly decreased MMP-14 expression in HNSCC 11A and especially 14C but not in CERV196 apart from an apoptotic process. 5-FU had no significant effect on MMP-14 expression independent of the HPV-status. Significant alterations of MMP-2 could be detected in HNSCC 11A only.

Conclusion: Although neither of the applied drugs were selective inhibitors of MMP-expression, surprisingly docetaxel significantly decreased MMP-14 in HNSCC 14C and 11A in this study. Interestingly, HPV-positive CERV196 was not sensitive to decreased MMP-14 or -2 expression following incubation with 5-FU or docetaxel.

Keywords: MMP-14; MMP-2; docetaxel; fluorouracil; head and neck squamous cell carcinoma.