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

Anna Ansell, Fredrik Jerhammar, Rebecca Ceder, Roland Grafström, Reidar Grénman, Karin Roberg (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

14 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)866-871
JournalOral Oncology
Volume45
Issue number10
DOIs
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed

Fingerprint

Matrix Metalloproteinase 7
Matrix Metalloproteinase 13
Head and Neck Neoplasms
Cisplatin
Gene Ontology
Matrix Metalloproteinases
Cell Line
Regulator Genes
Biomarkers
Chemoradiotherapy
Microarray Analysis
Computational Biology
Tumor Cell Line
Genes
Real-Time Polymerase Chain Reaction
Carcinoma, squamous cell of head and neck
Genome
Drug Therapy
Messenger RNA

Keywords

  • Predictive markers
  • Gene Ontology
  • Head and neck cancer
  • Cisplatin
  • Microarray
  • MMPs

Cite this

Ansell, Anna ; Jerhammar, Fredrik ; Ceder, Rebecca ; Grafström, Roland ; Grénman, Reidar ; Roberg, Karin. / Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines. In: Oral Oncology. 2009 ; Vol. 45, No. 10. pp. 866-871.
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abstract = "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.",
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Matrix metalloproteinase-7 and -13 expression associate to cisplatin resistance in head and neck cancer cell lines. / Ansell, Anna; Jerhammar, Fredrik; Ceder, Rebecca; Grafström, Roland; Grénman, Reidar; Roberg, Karin (Corresponding Author).

In: Oral Oncology, Vol. 45, No. 10, 2009, p. 866-871.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Jerhammar, Fredrik

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AU - Roberg, Karin

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