Angiogenesis and Lymphangiogenesis in Bladder Cancer

Abstract

In cancer patients, the majority of deaths occur as a consequence of metastatic diseases. In addition, metastasis is a marker for poor prognosis and low quality of life in many malignancies. Several groups have investigated the mechanism of tumor metastasis. Metastatic lesions are formed through a multi-step complex process and then spread either locally at the site of the primary tumor, or into distant organs through the blood or lymphatic vessels. Another important feature of cancers is the chaotic behavior of tumor growth and cancer cell cycle progression. To maintain such activities, abundant supply of oxygen and nutrients are necessary. Angiogenesis refers to the formation of new blood vessels and development of new branching vessels from the existing tumor tissue vasculature and this pathological process is important to secure adequate blood supply including oxygen and nutrients to the rapidly dividing malignant cells. In fact, there is a good correlation between tumor growth/cancer cell proliferation and the extent of angiogenesis in almost of all cancers. While there is abundant information on the mechanisms that are involved in the initiation, regulation and maintenance of angiogenesis in cancer tissue, little is known about the mechanisms involved in the formation of new lymphatic vessels (lymphangiogenesis) in cancers. Furthermore, the current knowledge about cancer dissemination through the lymphatics lacks details about the mode of transport of cancer cells within the lymphatic vessels and the mechanisms involved in their exit and seeding into the distant organs. In this paper, we review the clinical and pathological significance of angiogenesis and lymphangiogenesis in bladder cancer. In addition, the mechanisms that regulate the formation of new vessels in bladder cancer are discussed. Specifically, we focus on the factors that co-regulate these two different vessels and their potential use as predictive marker of outcome in patients with bladder cancer. In addition, we also discuss the limitation of quantification of these vessels in human tissues.