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siRNA and miRNA Gene Silencing

Volume 487 of the series Methods in Molecular Biology pp 1-24

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Targeting Stromal-cancer Cell Interactions with siRNAs

  • Seyedhossein AharinejadAffiliated withLaboratory for Cardiovascular Research, Center for Anatomy and Cell Biology, Medical University of Vienna
  • , Mouldy SioudAffiliated withDepartment of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital Email author 
  • , Trevor LucasAffiliated withLaboratory for Cardiovascular Research, Center for Anatomy and Cell Biology, Medical University of Vienna
  • , Dietmar AbrahamAffiliated withLaboratory for Cardiovascular Research, Center for Anatomy and Cell Biology, Medical University of Vienna

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Abstract

Tumors are composed of both malignant and normal cells, including fibroblasts, endothelial cells, mesenchymal stem cells, and inflammatory immune cells such as macrophages. These various stromal components interact with cancer cells to promote growth and metastasis. For example, macrophages, attracted by colony-stimulating factor-1 (CSF-1) produced by tumor cells, in turn produce various growth factors such as vascular endothelial growth factor, which supports the growth of tumor cells and their interaction with blood vessels leading to enhanced tumor cell spreading. The activation of autocrine and paracrine oncogenic signaling pathways by stroma-derived growth factors and cytokines has been implicated in promoting tumor cell proliferation and metastasis. Furthermore, matrix metalloproteinases (MMPs) derived from both tumor cells and the stromal compartment are regarded as major players assisting tumor cells during metastasis. Collectively, these recent findings indicate that targeting tumor–stroma interactions is a promising strategy in the search for novel treatment modalities in human cancer. This chapter summarizes our current understanding of the tumor microenvironment and highlights some potential targets for therapeutic intervention with small interfering RNAs.

Keywords

Stroma matrix metalloproteinases extracellular matrix colony-stimulating factor vascular endothelial growth factor tumor macrophages angiogenesis metastasis RNA interference small interfering RNAs