Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines

• Published in: Oral oncology 2009-10, Vol.45 (10), p.866-871
• Main Authors: Ansell, Anna, Jerhammar, Fredrik, Ceder, Rebecca, Grafström, Roland, Grénman, Reidar, Roberg, Karin
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cell Line, Tumor; Cisplatin; Cisplatin - therapeutic use; Drug Resistance, Neoplasm; Gene Ontology; Head and neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Hematology, Oncology and Palliative Medicine; Humans; Matrix Metalloproteinase 13 - metabolism; Matrix Metalloproteinase 7 - metabolism; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Microarray; Microarray Analysis; MMPs; Neoplasm Proteins - metabolism; Otolaryngology; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Predictive markers; Treatment Outcome; Tumors
• ISSN: 1368-8375; 1879-0593; 1879-0593
• DOI: 10.1016/j.oraloncology.2009.02.008

Summary Concomitant chemoradiotherapy is a common treatment for advanced head and neck squamous cell carcinomas (HNSCC). Cisplatin is the backbone of chemotherapy regimens used to treat HNSCC. Therefore, the aim of this study was to identify predictive markers for cisplatin treatment outcome in HNSCC. The intrinsic cisplatin sensitivity (ICS) was determined in a panel of tumour cell lines. From this panel, one sensitive and two resistant cell lines were selected for comparative transcript profiling using microarray analysis. The enrichment of Gene Ontology (GO) categories in sensitive versus resistant cell lines were assessed using the Gene Ontology Tree Machine bioinformatics tool. In total, 781 transcripts were found to be differentially expressed and 11 GO categories were enriched. Transcripts contributing to this enrichment were further analyzed using Ingenuity Pathway Analysis (IPA) for identification of key regulator genes. IPA recognized 20 key regulator genes of which five were differentially expressed in sensitive versus resistant cell lines. The mRNA level of these five genes was further assessed in a panel of 25 HNSCC cell lines using quantitative real-time PCR. Among these key regulators, MMP-7 and MMP-13 are implicated as potential biomarkers of ICS. Taken together, genome-wide transcriptional analysis identified single genes, GO categories as well as molecular networks that are differentially expressed in HNSCC cell lines with different ICS. Furthermore, two novel predictive biomarkers for cisplatin resistance, MMP-7 and MMP-13, were identified.