Endogenous Stimulators and Inhibitors of Angiogenesis in Gastrointestinal Cancers: Basic Science to Clinical Application  Malin Sund, Michael Zeisberg, Raghu Kalluri  Gastroenterology  Volume 129, Issue 6, Pages 2076-2091 (December 2005) DOI: 10.1053/j.gastro.2005.06.023 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 The characteristic features of normal blood vessels and tumor-associated blood vessels. The blood vessel wall consists of an EC lining, a VBM, and a supporting outer pericyte layer. Note that the pericytes can be in contact with the ECs through the BM, as determined by electron microscopy studies. Nevertheless, whether this actually happens in vivo still lacks solid experimental proof. The tumor vessels show irregularities in the vessel shape, loose EC connections, sparse pericyte coverage, and detached pericytes. In addition, many defects within the VBM, such as interruptions, multiple layers, and abnormal spikes, can be observed in blood vessels associated with tumors. Gastroenterology 2005 129, 2076-2091DOI: (10.1053/j.gastro.2005.06.023) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 The angiogenic balance. Angiogenesis stimulators such as VEGF, basic fibroblast growth factor, and platelet-derived growth factor, and angiogenesis inhibitors such as endostatin, tumstatin, TSP-1, and others maintain the angiogenic balance in the body. When the total activity of pro-angiogenic molecules exceeds that of the inhibitors, the anti-angiogenic balance is switched to favor new blood vessel formation. On the other hand, an excess of anti-angiogenic molecules would favor inhibition of angiogenesis. Whether the physiologic situation favors inhibition of angiogenesis or is in balance with angiogenesis stimulators is not known. Gastroenterology 2005 129, 2076-2091DOI: (10.1053/j.gastro.2005.06.023) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 3 The hypothesis that cancer progression likely is associated with emerging dependence on different pro-angiogenic factors. Fast-growing cancers such as colorectal cancer likely depend on 1 angiogenic factor such as VEGF, whereas slow-growing cancers such as breast cancer might undergo more genetic instability, favoring the use of several angiogenic factors for tumor growth,178 thus making it less likely for an agent that neutralizes 1 angiogenic factor to show clinical efficacy. Gastroenterology 2005 129, 2076-2091DOI: (10.1053/j.gastro.2005.06.023) Copyright © 2005 American Gastroenterological Association Terms and Conditions