Cancer as a metabolic disease : on the origin, management, and prevention by Thomas N. Seyfried

Author:Thomas N. Seyfried
Language: eng
Format: epub
Published: 2012-05-16T16:00:00+00:00

12.4 Sustained Vascularity (Angiogenesis)

Angiogenesis involves neovascularization or the formation of new capillaries from existing blood vessels and is associated with the processes of tissue inflammation, wound healing, and tumorigenesis [45–48]. Figure 1.3 highlights the role of angiogenesis in tumor progression. Angiogenesis is required for most tumors to grow beyond an approximate size of 0.2–2.0 mm [49]. This is necessary to provide the tumor with essential energy nutrients, including glucose and glutamine, and to remove toxic tumor waste products such as lactic acid and ammonia [3, 50].

In addition to its role in upregulating glycolysis in response to hypoxia, HIF-1α is also the main transcription factor for vascular endothelial growth factor (VEGF), which stimulates angiogenesis [15, 51–53] (see also Figs. 17.11 and 17.16). HIF-1α is part of the IGF-1/PI3K/Akt signaling pathway that also indirectly influences the expression of βfibroblast growth factor (FGF), another key angiogenesis growth factor [15, 54]. Many of the genes and metabolites that drive angiogenesis arise as secondary consequences of tumor cell fermentation. Hence, the sustained vascularity of tumors can be linked mechanistically to the metabolic requirements of fermentation and substrate-level phosphorylation necessary for tumor cell survival.

When viewed collectively, the information presented in this chapter provides compelling evidence linking several of the Hanahan and Weinberg hallmarks of cancer directly to insufficient respiration in tumor cells. It is also interesting that the cancer hallmarks discussed in this chapter are not unique to malignant cancers but are also present in benign tumors [55]. Indeed, abnormalities in growth control, telomerase activity, apoptosis, and angiogenesis are present in many tumors that do not invade or metastasize. Nevertheless, I think it is easy to see how respiratory insufficiency can account for these characteristics in tumors.

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