Angiogenic and lymphangiogenic cascades in the tumor microenvironment

Blood and lymphatic vessels in tumor tissue are major components of the tumor microenvironment. These vessels are newly formed from pre-existing host vessels stimulated by pro-blood-angiogenic and pro-lymphangiogenic (pro-blood/lymph-angiogenic) factors expressed in tumor cells. Tumor cells establish a specific stromal microenvironment fostering tumor growth, in which blood/lymph-angiogenesis are involved. The tumorassociated blood/lymph- angiogenesis is continually induced by complicated cytokine networks, namely problood/ lymph-angiogenic factor-mediated paracrine and autocrine interactions among tumor cells and stromal cells including endothelial cells (ECs) and non-endothelial mesenchymal cells (neMCs). In this review, we provide an overview of the features of tumor-associated blood/lymphangiogenesis based on recent and updated information obtained mainly from our studies. With regard to the constituent cell-dependent molecular mechanisms that regulate tumor blood/lymph-angiogenesis, we focus on: 1) the role of blood/lymph-angiogenesis- related factors/receptors expressed in tumor cells; and 2) the role of blood/lymph-angiogenesis-related factors/receptors expressed in stromal cells (ECs and neMCs). Finally, we discuss the features of tumor-associated blood/lymphanigogenesis, especially a vessel abnormality through the viewpoint of blood/lymph-angiogenic cascades in tumor microenvironment for better understanding of the tumor vascular biology.