Article

The fibroblastic coconspirator in cancer progression

Department of Anatomy, University of California, San Francisco, 94143-0452, USA.
Cold Spring Harbor Symposia on Quantitative Biology 02/2005; 70:383-8. DOI: 10.1101/sqb.2005.70.007
Source: PubMed

ABSTRACT A remarkable change has occurred in the thinking about epithelial-derived cancer in recent years: From almost entirely focusing on oncogenes and tumor suppressor genes has come the realization that the tumor microenvironment is a coconspirator in the carcinogenic process. Many types of stromal cells, including fibroblasts, adipocytes, macrophages, mast cells, and cells of the vascular system, are crucial contributors to epithelial carcinogenesis. Here, we focus on the fibroblast's role in cancer progression and the molecules involved in the communications between the fibroblasts and the cancer cells, including fibroblast secreted protein 1 (FSP-1 or S100A4), transforming growth factor beta (TGF-beta), the chemokine CXCL-12 (stromal derived factor 1 alpha, SDF-1alpha), type I collagen, and matrix metalloproteinase 13 (MMP-13).

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    • "It is well known that a large component of solid tumors is made up of stromal cells and may consist of a variety of different cell types, including inflammatory cells, vascular endothelial cells and fibroblasts. In fact these stromal cells are essential for tumor growth, mediated either through direct cell contacts and/or secreted factors [17] [18]. In an effort to understand the role of the micro-environment [19], a study was conducted wherein they compared the gene expression profiles of neoplastic stromal cells versus stromal cells from non-tumor skin. "
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    • "It is well known that a large component of solid tumors is made up of stromal cells and may consist of a variety of different cell types, including inflammatory cells, vascular endothelial cells and fibroblasts. In fact these stromal cells are essential for tumor growth, mediated either through direct cell contacts and/or secreted factors [17] [18]. In an effort to understand the role of the micro-environment [19], a study was conducted wherein they compared the gene expression profiles of neoplastic stromal cells versus stromal cells from non-tumor skin. "
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    • "It is also clear that the MMP activity around a tumor is a feature of increased tissue remodeling as much as increased tissue degradation. Although modifications or degradation of the ECM by tumor-derived proteases was originally thought to destroy physical barriers to cell migration, more recently profound effects on cell adhesion and migration were identified, related to MMP activation on various tissue culture substrates including fibronectin, gelatin, and vitronectin (Egeblad et al., 2005; Kessenbrock et al., 2010; Peng et al., 2011). On the other hand, recent findings also suggest that excessive proteolysis may inhibit this process by impairing tumor cell adhesion or disrupting and degrading the cell-matrix interactions or matrix signals required for migration and invasion, demonstrating the existence of a certain critical range or a balance between some MMPs and TIMP expression in order for both tumor invasion and angiogenesis to occur (Seo et al., 2003; Chernov et al., 2009). "
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