II. Pericytes and vasculature
The role of normal vasculature is to provide tissues and organs with blood supply and nutrients. Pericytes are elongated fairly undifferentiated mural cells that line the arterioles and epithelium outside the basement membrane. Endothelial cells shape the lining of the vascular tube, while, mural cells associate with the exterior of the tube. Pericytes are involved in the regulation of blood flow and the transformation of new blood vessels. Typically, pericytes colocalize with capillaries and they play an important role in the process of vascular maturation and stabilization. Classified as either smooth muscle cells or pericytes, mural cells are identified based on the types of vessels they are connected with and what molecular markers they express [1, 2]. It is well known that Regulator of G-protein Signaling 5 (RGS-5) is expressed in pericytes of vessels undergoing angiogenesis. .
In a study that used the growth factor sphingosine-1-phospate (S1P) to stimulate cultured vascular smooth muscle cells, RGS-5 expression was constrained to the leading edge of migrating pericytes. This restriction of RGS-5 greatly reduced cell migration suggesting that RGS-5 may control the inhibitory response of pericytes to growth factors leading to vessel stabilization. Interestingly, the animals in our study carrying a tumor xenograft with induced RGS5 over-expression tended to show a more stable tumor, and had a better survival outcome. In the essential process of pericyte recruitment to endothelial cells during development, RGS5 has shown the ability to regulate PDGFR-β signaling in vitro. This further goes along with the potential role of RGS-5 during pericyte migration. Interestingly, it is known that a number of RGS5 proteins can hinder chemoattractant receptors and control cellular processes such as migration and adhesion. G protein-coupled receptor signaling is thought to be inhibited by the up-regulation of RGS-5 in the course of vascular maturation. RGS5 possibly inhibits GPCR signaling by accelerating the transition state of Gα subunits from the active GTP to the inactive GDP-bound state causing pericytes to be less receptive to chemokine signaling [2, 3].
III. Angiogenesis in Cancer
Angiogenesis is a vital process for sustained growth and development in the human body. In its normal state angiogenesis is tightly synchronized and spurs new blood vessels in orderly matrices. However, in cancer the process of angiogenesis is unregulated and can result in an aberrant network of blood vessels within a solid tumor. These changes in vasculature greatly affect the tumor microenvironment and landscaping within the tumor that ultimately dictate a tumor’s progression and response to anticancer therapy. Like weeds, tumor cells have the capacity to more aggressively proliferate than the cells that form blood capillaries; the rapid proliferation of tumor cells forces vessels apart. The disordered...