The Role of Tumor Stroma in Cancer Progression and Prognosis: Emphasis on Carcinoma-Associated Fibroblasts and Non-small Cell Lung Cancer Roy M. Bremnes,

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The Role of Tumor Stroma in Cancer Progression and Prognosis: Emphasis on Carcinoma-Associated Fibroblasts and Non-small Cell Lung Cancer Roy M. Bremnes, MD, PhD, Tom Dønnem, MD, PhD, Samer Al-Saad, MD, PhD, Khalid Al-Shibli, MD, PhD, Sigve Andersen, MD, Rafael Sirera, MSc, PhD, Carlos Camps, MD, PhD, Inigo Marinez, MSc, PhD, Lill-Tove Busund, MD, PhD Journal of Thoracic Oncology Volume 6, Issue 1, Pages 209-217 (January 2011) DOI: 10.1097/JTO.0b013e3181f8a1bd Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Crosstalk (efferent and afferent signaling) between the normal epithelial cells and the stromal cells (blue arrows) maintains tissue equilibrium and integrity (green arrow). During epithelial carcinogenesis, the efferent signaling changes (orange arrow). This leads to alterations in the stroma. The new established crosstalk (dashed blue arrow) between tumor cells and cells of the tumor stroma leads to invasion and subsequently to metastasis (red arrow). Adapted from J Pathol. 2003;200:429–447. Journal of Thoracic Oncology 2011 6, 209-217DOI: (10.1097/JTO.0b013e3181f8a1bd) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Efferent signaling from carcinoma-associated fibroblast in the tumor stroma. The fibroblasts communicate with malignant cells, epithelial cells, endothelial cells, pericytes, and inflammatory cells through the secretion of several growth factors and chemokines. Adapted from Nat Rev Cancer. 2006;6:392–401; Curr Opin Genet Dev. 2009;19:67–73; and Semin Cell Dev Biol. 2010;21:33–39. CCL, chemokine ligand; CXCL, chemokine ligand; CTGF, connective tissue growth factor; EGF, epithelial growth factor; FGF2, fibroblast growth factor 2; IGF-1, insulin-like growth factor-1; HGF, hepatocyte growth factor; IL, interleukin; MMPs, matrix metalloproteinases; SFRP1, secreted frizzled-related protein 1; TGF, transforming growth factor; VEGF, vascular endothelial growth factor. Journal of Thoracic Oncology 2011 6, 209-217DOI: (10.1097/JTO.0b013e3181f8a1bd) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions