Abnormalities of Pericytes on Tumor Blood Vessels

Blood vessels in tumors have multiple abnormalities. They are unusually dynamic, and naturally undergo sprouting, proliferation, remodeling, or regression. The vessels are irregularly shaped, tortuous, and lack the normal hierarchical arrangement of arterioles, capillaries, and venules. Endothelial cells in tumors have abnormalities in gene expression, require growth factors for survival, and have defective barrier function to plasma proteins. Whether pericytes are even present on tumor vessels has been disputed. Recent evidence, however, indicates they are indeed present but exhibit multiple abnormalities. In some cases, absence of expression of a marker such as α‐smooth muscle actin (αSMA) explains why pericytes may be missed by conventional immunohistochemical staining. By using confocal microscopy to analyze the 3‐dimensional structure of blood vessels in multiple different mouse tumors stained for the pericyte markers, αSMA, desmin, NG2, and platelet derived growth factor (PDGF) receptor‐β, we found pericytes are consistently present on tumor vessels but are loosely attached to endothelial cells, have abnormal shapes, or may extend cytoplasmic processes away from the vessel wall. The functional consequences of the loose attachment is still unclear, but they may include weakening of the vessel wall, predisposition to hemorrhage, and impaired vasomotor tone. Such abnormalities are consistent with alterations in PDGF signaling. Use of selective PDGF antagonists has shown that pericytes in some tumors are unusually dependent on PDGF signaling for survival. Loss of pericytes can lead to destabilization and regression of tumor vessels. Pericyte abnormalities can thus be exploited as targets of angiogenesis inhibitors in the treatment of cancer.