Expression profiles and clinical correlations of degradome components in the tumor microenvironment of head and neck squamous cell carcinoma

Angela Stokes, Juho Joutsa, Risto Ala-aho, Mark Pitchers, Caroline J. Pennington, Craig Martin, Don J. Premachandra, Yasunori Okada, Juha Peltonen, Reidar Grénman, Helen A. James, Dylan R. Edwards, Veli Matti Kähäri

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Abstract

Purpose: Head and neck squamous cell carcinomas (HNSCC) are characterized by high morbidity and mortality, largely due to the high invasive and metastatic potential of these tumors, high recurrence rates, and low treatment responses. Proteinases have been implicated in several aspects of tumor growth and metastasis in a broad range of tumors including HNSCC. Experimental Design: Comprehensive expression profiling of proteinases [matrix metalloproteinases (MMPs), A disintegrin and metalloproteinase (ADAMs), and ADAMs with thrombospondin motif (ADAMTSs)] and their inhibitors [tissue inhibitor of metalloproteinases (TIMPs)] was done using quantitative real-time reverse transcription-PCR analysis of a large cohort of tissue samples representing the tumor (n = 83), the invasive margin (n = 41), and the adjacent tissue (n = 41) from 83 HNSCC patients, along with normal tissue controls (n = 13), as well as cell lines established from tumors of 34 HNSCC patients. Results: The results show specifically elevated gene expression of several proteinases, including MMP1, MMP3, MMP10, and MMP13 within tumor tissue and peritumoral adjacent tissue. In addition, the results identify several novel HNSCC-associated proteinases, including ADAM8, ADAM9, ADAM17, ADAM28, ADAMTS1, ADAMTS8, and ADAMTS15. There were also significant differences in proteinase expression based on clinical parameters, i.e., tumor location, grade, and local invasion. MMP13 expression was significantly higher in large (>4 cm) locally invasive tumors (P < 0.05). MMP9 expression was significantly decreased in tumors with regional metastasis, whereas increased expression of ADAM8 was noted in the metastatic tumors (P < 0.001 for both). Conclusions: These findings suggest the HNSCC degradome as a valuable source of diagnostic, predictive, and prognostic molecular markers for these malignant tumors.

Original languageEnglish
Pages (from-to)2022-2035
Number of pages14
JournalClinical Cancer Research
Volume16
Issue number7
DOIs
Publication statusPublished - 2010 Apr 1

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Tumor Microenvironment
Peptide Hydrolases
Neoplasms
Disintegrins
Metalloproteases
Neoplasm Metastasis
Thrombospondins
Carcinoma, squamous cell of head and neck
Tissue Inhibitor of Metalloproteinases
Tumor Biomarkers
Tumor Cell Line
Matrix Metalloproteinases
Reverse Transcription
Research Design
Morbidity
Gene Expression
Recurrence
Polymerase Chain Reaction
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression profiles and clinical correlations of degradome components in the tumor microenvironment of head and neck squamous cell carcinoma. / Stokes, Angela; Joutsa, Juho; Ala-aho, Risto; Pitchers, Mark; Pennington, Caroline J.; Martin, Craig; Premachandra, Don J.; Okada, Yasunori; Peltonen, Juha; Grénman, Reidar; James, Helen A.; Edwards, Dylan R.; Kähäri, Veli Matti.

In: Clinical Cancer Research, Vol. 16, No. 7, 01.04.2010, p. 2022-2035.

Research output: Contribution to journalArticle

Stokes, A, Joutsa, J, Ala-aho, R, Pitchers, M, Pennington, CJ, Martin, C, Premachandra, DJ, Okada, Y, Peltonen, J, Grénman, R, James, HA, Edwards, DR & Kähäri, VM 2010, 'Expression profiles and clinical correlations of degradome components in the tumor microenvironment of head and neck squamous cell carcinoma', Clinical Cancer Research, vol. 16, no. 7, pp. 2022-2035. https://doi.org/10.1158/1078-0432.CCR-09-2525
Stokes, Angela ; Joutsa, Juho ; Ala-aho, Risto ; Pitchers, Mark ; Pennington, Caroline J. ; Martin, Craig ; Premachandra, Don J. ; Okada, Yasunori ; Peltonen, Juha ; Grénman, Reidar ; James, Helen A. ; Edwards, Dylan R. ; Kähäri, Veli Matti. / Expression profiles and clinical correlations of degradome components in the tumor microenvironment of head and neck squamous cell carcinoma. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 7. pp. 2022-2035.
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AU - Joutsa, Juho

AU - Ala-aho, Risto

AU - Pitchers, Mark

AU - Pennington, Caroline J.

AU - Martin, Craig

AU - Premachandra, Don J.

AU - Okada, Yasunori

AU - Peltonen, Juha

AU - Grénman, Reidar

AU - James, Helen A.

AU - Edwards, Dylan R.

AU - Kähäri, Veli Matti

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