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Review
. 2018 Mar;12(1):171-179.
doi: 10.1007/s12079-017-0433-3. Epub 2017 Dec 20.

Integration of pro- and anti-angiogenic signals by endothelial cells

Shideh Kazerounian  1 , Jack Lawler  2
Affiliations
Review

Integration of pro- and anti-angiogenic signals by endothelial cells

Shideh Kazerounian et al. J Cell Commun Signal. 2018 Mar.

Abstract

Angiogenesis or neovascularization is a complex multi-step physiological process that occurs throughout life both in normal tissues and in disease. It is tightly regulated by the balance between pro-angiogenic and anti-angiogenic factors. The angiogenic switch has been identified as the key step during tumor progression in which the balance between pro-angiogenic and anti-angiogenic factors leans toward pro-angiogenic stimuli promoting the progression of tumors from dormancy to dysplasia and ultimately malignancy. This event can be described as either the outcome of a genetic event occurring in cancer cells themselves, or the positive and negative cross-talk between tumor-associated endothelial cells and other cellular components of the tumor microenvironment. In recent years, the mechanisms underlying the angiogenic switch have been extensively investigated in particular to identify therapeutic targets that can lead to development of effective therapies. In this review, we will discuss the current findings on the regulatory pathways in endothelial cells that are involved in the angiogenic switch with an emphasis on the role of anti-angiogenic protein, thrombospondin-1 (TSP-1) and pro-angiogenic factor, vascular endothelial growth factor (VEGF).

Keywords: TSP-1; VEGF; angiogenesis; cancer; dormancy; thrombospondin-1; vascular endothelial growth factor.

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Figures

Fig. 1
Fig. 1
The structure of TSP-1. The various domains of TSP-1 are shown and the sequence of the second TSR is written out. The sequence of the peptides that have been shown to inhibit angiogenesis in various models are listed below the sequence of the TSR. The fact that non-overlapping sequences are active suggests that the protein folds to bring these sites into proximity. A schematic diagram of the structure of the second TSR is shown at the right
Fig. 2
Fig. 2
Schematic representation of the anti- and pro-angiogenic signaling pathways involved in response to TSP-1 and VEGFA
Fig. 3
Fig. 3
Temporal regulation of the pathways that are regulated by VEGFA and TSP-1
See this image and copyright information in PMC

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