Angiogenesis, the formation of new blood vessels from the pre-existing
vasculature, is one main mechanism of vascularisation during the embryonic
development, growth, regeneration, wound healing and some physiological
processes such as formation of the corpus luteum and endometrium. On the other
hand, angiogenesis is also involved in a number of pathological processes such as
tumor growth, and metastasis. The tumour angiogesis process is believed to be
dependent on an ‘angiogenic switch’ formed and a cascade of biologic events as a
consequence of the “cross-talk” between tumor cells and several components of
local microenvironment including endothelial cells, macrophages, mast cells and
stromal components. In this context, a growing body of evidences supports the role
of ligands/RAGE axis in angiogenesis. Upon RAGE engagement, profound effects
are reported not only in endothelial cells but also in endothelial progenitor cells and
many immune cells located at tumor microenvironment, thus turning on the
angiogenic switch. The present review to highlight the mechanisms by which RAGE
engagement promotes many changes, in both tumor and host cells, leading to the
formation of new blood vessels. Finally, some potential pharmacological
approaches to circumvent the deleterious effects of RAGE engagement are also
discussed; mainly focused on those directed to inhibit or destroy RAGE ligands,
such as the use amadorins, inhibitors of AGE formation and cross-link breakers; as
well as those approaches targeting RAGE activation, either by blocking RAGE
binding, or down-regulating its expression.
Keywords: Angiogenesis, advanced glycation, tumor microenvironment, tumor biology.
