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Review
. 2011 Dec 15;71(24):7339-44.
doi: 10.1158/0008-5472.CAN-11-1718. Epub 2011 Dec 5.

The Evolution of Endothelial Regulatory Paradigms in Cancer Biology and Vascular Repair

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Free PMC article
Review

The Evolution of Endothelial Regulatory Paradigms in Cancer Biology and Vascular Repair

Joseph W Franses et al. Cancer Res. .
Free PMC article

Abstract

Although the roles of endothelial cells in cancer have primarily been considered to be related to tumor perfusion, the emerging appreciation of "angiocrine" regulation adds stromal regulatory capabilities to the expanding list of endothelial functions in tumors. We posit that an understanding of the state-dependent paracrine regulatory paradigms established in vascular disease and repair will be critical for a deep understanding of tumor biology, as endothelial cells regulate diverse processes in all vascularized tissues. Here, we outline the historical developments that led to the appreciation of the paracrine regulatory functions of endothelial cells, summarize classical views of blood vessels and stroma in cancer, and attempt to merge these ideas to include the stromal regulatory endothelial cell as a critical regulator of cancer. The notion of the endothelial cell as a biochemical regulator of cancer state in constant dynamic balance with its tumor could impact diagnosis, prognosis, and treatment of cancer. Such concepts might well explain the mixed results from antiangiogenic cancer therapeutics and how certain drugs that improve vascular health correlate with improved cancer prognosis.

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Figure 1
Figure 1. Evolution of endothelial regulatory roles in vascular repair and homologies with roles in cancer
(A) The endothelium, the cellular lining of the vasculature, is a remarkably plastic and responsive organ with far-reaching regulatory roles. (B) State-dependent regulatory paradigms identified in vascular disease and repair may be useful as guides for the examination of endothelial roles in cancer.

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