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Int. J. Mol. Sci. 2017, 18(11), 2355; https://doi.org/10.3390/ijms18112355

Collateral Damage Intended—Cancer-Associated Fibroblasts and Vasculature Are Potential Targets in Cancer Therapy

Institute of Physiological Chemistry and Pathobiochemistry, Münster University Hospital, 48149 Münster, Germany
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Received: 28 September 2017 / Revised: 25 October 2017 / Accepted: 2 November 2017 / Published: 7 November 2017
(This article belongs to the Special Issue Chemical and Molecular Approach to Tumor Metastases)
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Abstract

After oncogenic transformation, tumor cells rewire their metabolism to obtain sufficient energy and biochemical building blocks for cell proliferation, even under hypoxic conditions. Glucose and glutamine become their major limiting nutritional demands. Instead of being autonomous, tumor cells change their immediate environment not only by their metabolites but also by mediators, such as juxtacrine cell contacts, chemokines and other cytokines. Thus, the tumor cells shape their microenvironment as well as induce resident cells, such as fibroblasts and endothelial cells (ECs), to support them. Fibroblasts differentiate into cancer-associated fibroblasts (CAFs), which produce a qualitatively and quantitatively different extracellular matrix (ECM). By their contractile power, they exert tensile forces onto this ECM, leading to increased intratumoral pressure. Moreover, along with enhanced cross-linkage of the ECM components, CAFs thus stiffen the ECM. Attracted by tumor cell- and CAF-secreted vascular endothelial growth factor (VEGF), ECs sprout from pre-existing blood vessels during tumor-induced angiogenesis. Tumor vessels are distinct from EC-lined vessels, because tumor cells integrate into the endothelium or even mimic and replace it in vasculogenic mimicry (VM) vessels. Not only the VM vessels but also the characteristically malformed EC-lined tumor vessels are typical for tumor tissue and may represent promising targets in cancer therapy. View Full-Text
Keywords: abnormal tumor vasculature; anti-angiogenesis; cancer-associated fibroblasts; endothelial cell–tumor cell interaction; targeted tumor therapy; tumor neovascularization; tumor metabolism; tumor stroma; tumor vessel disruption; vasculogenic mimicry abnormal tumor vasculature; anti-angiogenesis; cancer-associated fibroblasts; endothelial cell–tumor cell interaction; targeted tumor therapy; tumor neovascularization; tumor metabolism; tumor stroma; tumor vessel disruption; vasculogenic mimicry
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Cavaco, A.; Rezaei, M.; Niland, S.; Eble, J.A. Collateral Damage Intended—Cancer-Associated Fibroblasts and Vasculature Are Potential Targets in Cancer Therapy. Int. J. Mol. Sci. 2017, 18, 2355.

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