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Cytokines and Receptors in Angiogenesis

Chronic inflammation may be an underlying factor promoting the pathogenesis of a variety of diseases. Pro-inflammatory cytokines and chemokines, including IL-1, IL-6, IL-8, and TNF-alpha establish an environment that promotes disease progression. These cytokines and chemoattractants are secreted by immune regulatory cells, but also by tumor cells, tumor-associated macrophages, and stromal cells. In addition, tumor-associated cells secrete growth factors, such as VEGF and FGF basic, and matrix-degrading proteases. Together these factors establish a microenvironment that promotes tumor progression by stimulating processes such as angiogenesis, invasion, and metastasis. Importantly, cytokines secreted by tumor cells also recruit tumor infiltrating leukocytes. These leukocytes can produce either pro- or anti-tumorigenic/angiogenic cytokines, which will also play a role in determining how tumor growth is affected.

Other conditions associated with chronic inflammation, such as obesity, also lead to alterations in the levels of specific cytokines. Leptin, Hepatocyte Growth Factor (HGF), and Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) are three cytokines secreted by adipose tissue or adipose-associated macrophages that are elevated in obese individuals. Overexpression of these cytokines has detrimental cellular effects that include stimulating proliferation and angiogenesis. In contrast, Adiponectin, which is reduced in obesity, negatively regulates these processes by inducing endothelial cell apoptosis. Changes in cytokine levels may help to explain the link between obesity and certain forms of cancer.