Role of Vascular Leukocytes in Ovarian Cancer Neovascularization

Tumor angiogenesis is a process that allows primary tumors to grow beyond the approximate size of 1–2mm³. It has been shown that if cancer cells are placed in an avascular site like rabbit cornea, and the capillaries are physically prevented from reaching the implant or were inhibited from undergoing angiogenesis, tumor growth is dramatically impaired, restricting the tumor size to 0.4mm (15). In the absence of adequate vasculature, tumor cells become apoptotic or necrotic (4). It is now wellaccepted that antiangiogenic therapy, originally proposed by Judah Folkman (14), is a promising strategy against cancer. Recent trials with bevacizumab, an antibody against vascular endothelial growth factor (VEGF) used alone or in combination with chemotherapy, showed that systemic antiangiogenic therapy may indeed have a measurable impact on cancer progression and patient survival (31).

During embryogenesis, the formation and remodeling of new blood vessels occurs in two different ways: (1) angiogenesis-new vessels sprout and mature from preexisting vasculature, and (2) vasculogenesis-the new vessels are born from progenitor cells. In adults, new vessels are produced physiologically only via angiogenesis. For example in females, reproductive organs are formed during the follicular and menstrual cycles. Adult neovascularization occurs largely under pathologic situations, such as wound healing and tumor growth. The vascularization in malignant tumors happens through several different mechanisms, which are not mutually exclusive and very often occur concurrently (10, 17).