Angiogenesis, or the expansion of new blood vessels from pre-existing vessels is a crucial and normal multi-step process which occurs during the course of embryogenesis, helping to form the vascular network during development and acting as a repair mechanism during adult life. When this process becomes dysregulated it can affect our health and is associated with the development of a number of important diseases including cancer, psoriasis, blindness and arthritis as well as more common diseases such as asthma, artherosclerosis and obesity. Over the past 30 years the role of angiogenesis in cancer has been ever increasing area of research, beginning with the revolutionary ideas of Judah Folkman who postulated that tumor growth is angiogenesis dependent. Through such work we now know that tumors express many factors including vascular endothelial growth factor(VEGF) and its receptor(VEFGR), fibroblast growth factor (FGF)-1, FGF-2, angiopoietin-1 and 2, placenta growth factor and hypoxia-inducible factor (HIF)-1α which can mediate angiogenesis. For example, VEGF is known to play an important role in the initial steps of angiogenesis, through the activation of signaling pathways leading to vasodilation, increased vascular permeability and the survival, proliferation and migration of endothelial cells. Furthermore, clinical studies suggest that VEGF expression is positively correlated with tumor size, tumor grade and unfavourable prognosis; underscoring its central role in disease.
Abnormal vasculature is associated with a number of human diseases and is considered a hallmark of solid tumors. Here, in contrast to the hierarchal and organized branching patterns seen in normal blood vessels, the branching pattern of tumor blood vessels is chaotic and vessel diameter irregular. Additionally, tumor-associated periocytes, which provide structural support to vessels and are themselves a source of VEFG have been shown to have an altered morphology and looser associations with endothelial cells. These important differences in structure and function are thought result in chaotic blood flow and leaky blood vessels, which can release plasma fluid into the tumor interstation and contribute to observed increases in tumor hydrostatic pressure.
Additionally, emerging evidence points towards a pivotal role for angiopoietins in the regulation of vessel growth and regression during normal and pathological angiogenesis, through the control of vessel stabilization and maturation.
Hypoxia is known to be a major driving factor behind angiogenesis. Here, low oxygen pressure drives the expansion of the vascular bed initially through simple diffusion and later through signaling via hypoxia-inducible transcription factors which transcriptionally regulate angiogenic factors such as Ang-2, VEGF and PDFG when tissue growth exceeds the limit of oxygen diffusion. Angiogenesis plays a central role in the growth and spread of cancer. As new blood vessels form, tumors are supplied with oxygen and nutrients, enabling invasive tissue growth and metastasis to occur.
A wealth of evidence implicates angiogenesis in the promotion of diseases such as cancer. Furthermore, recent evidence indicates that the local balance of proangiogenic and antiangiogenic factors are central to the “angiogenic switch” that tumors make. Bearing this in mind, a variety of strategies are currently being evaluated for their efficacy in inhibiting angiogenesis in a variety of human cancers.
Characteristics of angiogenic blood vessels in cancer animation
Angiogenesis is the process by which new blood vessels form within the body. In cancer, factors can be released that promote the formation of blood vessels in and around a tumor, supplying it with its own blood supply. The presence of these blood vessels is often correlated with a poor prognosis in patients with cancer. This medical animation describes the structure of these new blood vessels and some of the issues associated with tumor angiogenesis. This animation forms part of a larger web based project that Random42 developed to increase the awareness of cancer driven angiogenesis. This can be viewed by clicking on the following link: http://angiogenesis.amgen.com/
This is an image of an angiogenic blood vessel with loose tumor vessel endothelial cell associations; resulting in leaking tumor vasculature and the release of plasma fluid into the tumor interstitium which contributes to high tumor interstitium pressure.
This is an image depicting the tortuous, variable vessel diameter, and irregular branching pattern commonly seen in the vasculature of tumors.