Targeting stromal-cancer cell interactions with siRNAs.

Laboratory for Cardiovascular Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
Methods in Molecular Biology (Impact Factor: 1.29). 02/2009; 487:243-66. DOI: 10.1007/978-1-60327-547-7_12
Source: PubMed

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.

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    • "Recent studies demonstrated that the tumor stroma does not exist simply as a passive support structure, but rather plays an active role in tumor progression (Blavier and Declerck, 2005; Derynck et al., 2001; Shekhar et al., 2001). In fact, the activation of autocrine and paracrine signaling pathways by stromaderived cytokines and growth factors has been implicated in promoting tumor cell proliferation and metastasis (Aharinejad et al., 2009). Therefore, elements of the tumor microenvironment are promising targets for novel therapies that may overcome many of the limitations of current treatment options that are primarily targeted to the cancer cell. "
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