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Tumor–stroma interactions influence cytokine expression and matrix metalloproteinase activities in paired primary and metastatic head and neck cancer cells

Authors

  • Sittichai Koontongkaew,

    Corresponding author
    1. Faculty of Dentistry, Thammasat University, Klong Luang, Pathum, Tani 12121, Thailand
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  • Panomwat Amornphimoltham,

    Corresponding author
    1. Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20882, USA
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  • Bunjird Yapong

    Corresponding author
    1. Department of Oral Biology and Occlusion, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand
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Thammasat University, Faculty of Dentistry, 99 Moo 18 Paholyothin Road, Klong Luang, Pathum-Tani 12121, Thailand. Tel./fax: +66 2 516 5385. E-mail addresses: koontongkaew@yahoo.com

E-mail addresses: pamornph@mail.nih.gov

E-mail addresses: bunjerd.y@psu.ac.th

Abstract

This study evaluates the effects of gingival fibroblasts, type I collagen and autocrine/paracrine elements on cytokine expression in paired primary and metastatic human squamous cell carcinoma (HNSCC) cell lines. Additionally, the effects of IL-1α, IL-1β, IL-6, TNF-α, TGF-β and HGF on MMPs and cell invasion were investigated. RT-PCR results indicated the presence of mRNAs for IL-1α, IL-1β, IL-6, TNF-α, and TGF-β in primary and metastatic HNSCC cell lines but high expression of cytokines was not a prerequisite for metastatic cancer cells. HGF mRNA was not detected in the cancer cell lines. Co-culturing of HNSCC cells with fibroblasts caused increases in cytokine expression. Type I collagen and conditioned media derived from HNSCC cells or fibroblasts enhanced cytokine expression in the cancer cells. Cytokines also enhanced MMP-2 and MMP-9 enzymatic activities as well as HNSCC cell invasion. Our findings suggest that the interactions between cancer cells, the extracellular matrix and fibroblasts, as mediated by cytokines, play important roles in the progression of HNSCC.

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