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Vascular remodeling in cancer

Abstract

The growth and dissemination of tumors rely on an altered vascular network, which supports their survival and expansion and provides accessibility to the vasculature and a route of transport for metastasizing tumor cells. The remodeling of vascular structures through generation of new vessels (for example, via tumor angiogenesis) is a well studied, even if still quite poorly understood, process in human cancer. Antiangiogenic therapies have provided insight into the contribution of angiogenesis to the biology of human tumors, yet have also revealed the ease with which resistance to antiangiogenic drugs can develop, presumably involving alterations to vascular signaling mechanisms. Furthermore, cellular and/or molecular changes to pre-existing vessels could represent subtle pre-metastatic alterations to the vasculature, which are important for cancer progression. These changes, and associated molecular markers, may forecast the behavior of individual tumors and contribute to the early detection, diagnosis and prognosis of cancer. This review, which primarily focuses on the blood vasculature, explores current knowledge of how tumor vessels can be remodeled, and the cellular and molecular events responsible for this process.

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Abbreviations

BMD:

bone marrow-derived

EC:

endothelial cell

EPC:

endothelial progenitor cell

HEV:

high endothelial venule

LN:

lymph node

SLN:

sentinel LN

VEGF:

vascular endothelial growth factor

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Acknowledgements

MGA and SAS are supported by Research Fellowships and a Program Grant from the National Health and Medical Research Council of Australia. We apologize to authors whose work could not be quoted due to space limitations.

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MGA and SAS are shareholders of Circadian Technologies, which has a commercial interest in antiangiogenesis and antilymphangiogenesis in cancer, and Ark Therapeutics, which has an interest in the application of growth factors in vascular disease. RHF and ML declare no conflict of interest.

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Farnsworth, R., Lackmann, M., Achen, M. et al. Vascular remodeling in cancer. Oncogene 33, 3496–3505 (2014). https://doi.org/10.1038/onc.2013.304

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