J Cancer 2011; 2:478-483. doi:10.7150/jca.2.478
Short Research Communication
The First Type III Domain of Fibronectin is Associated with the Expression of Cytokines within the Lung Tumor Microenvironment
1. Center for Cell Biology and Cancer Research, Albany Medical College, Albany, New York, USA
2. Department of Pathology, Albany Medical College, Albany, New York, USA
Zheng M, Jones DM, Horzempa C, Prasad A, McKeown-Longo PJ. The First Type III Domain of Fibronectin is Associated with the Expression of Cytokines within the Lung Tumor Microenvironment. J Cancer 2011; 2:478-483. doi:10.7150/jca.2.478. Available from http://www.jcancer.org/v02p0478.htm
Recent studies have pointed to changes in tissue mechanics as a contributory element to the development of malignancies. Increased tissue rigidity is associated with the unfolding of the Type III domains of fibronectin within the extracellular matrix. The consequences of this unfolding on cellular functions within the lung are not well understood. In the present study, we evaluated the effect of a peptide representing a partially unfolded intermediate of the first Type III repeat of fibronectin (FnIII-1c) on inflammatory gene expression in adult human lung fibroblast cells. FnIII-1c induced expression of cytokines, CXCL1-3, IL-8 and TNF-α, by lung fibroblast cells. The increase in IL-8 expression was dependent on Toll-like receptor 2 and NFκB. Immunohistochemistry of tissue arrays representing squamous cell carcinoma of the lung revealed extensive stromal staining for IL-8 and fibronectin fibrils which were co-aligned with myofibroblasts. These data suggest a model in which unfolding of FnIII domains secondary to myofibroblast-generated tension may induce the release of cytokines by stromal fibroblasts present within the lung tumor.
Keywords: lung cancer, inflammation, fibronectin, cytokine