Molecular mechanisms of lymphangiogenesis in development and cancer

Abstract

The lymphatic system, also named the second vascular system, plays a critical role in tissue homeostasis and immunosurveillance. The past two decades of intensive research have led to the identification and detailed understanding of many molecular players and mechanisms regulating the formation of the lymphatic vasculature during embryonic development. Furthermore, clinical and experimental data clearly demonstrate that the formation of new lymphatic vessels by sprouting lymphangiogenesis from pre-existing lymphatic vessels, or by the de novo formation of lymphatic capillaries also occurs in various pathological conditions, such as cancer and organ transplant rejection, while lymphangiogenesis is non-functional in primary edema. In cancer, lymphatic vessels are one major gateway for invasive tumor cells to leave the primary tumor site and to establish distant organ metastasis. Therefore, the specific targeting of the lymphatic vasculature at the tumor site could be a promising approach to prevent metastasis formation.

SIX1 Promotes Tumor Lymphangiogenesis by Coordinating TGFβ Signals That Increase Expression of VEGF-C

“…Similar to tumor angiogenesis, lymphangiogenesis is mainly influenced by the tumor microenvironment (3). Among a variety of factors, VEGF-C and VEGF-D are considered the key drivers of lymphangiogenesis (4)(5)(6)(7)(8).…”

Prospero homeobox 1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis

“…PROX1 knockdown decreased the expression of lymphangiogenic inducers VEGF-C, VEGF-D, and COX-2 in human gastric cancer cells. Previous studies have shown that VEGF-C and VEGF-D induce the proliferation and migration of LECs by activating VEGFR-3, and that overexpression of VEGF-C, VEGF-D, or VEGFR-3 is associated with lymphatic metastasis and poor clinical outcomes of various cancers [25][26][27]. Further, COX-2 promotes tumor lymphangiogenesis and lymph node metastasis [28].…”

Cardiac Vasculature: Development and Pathology

“…The aorta (ao) and pulmonary artery (pa) are indicated at a low magnification (A, 100x) and higher magnifications are in (B, 200x) and (C, 400x) (Barbosky et al, 2006). (Albrecht and Christofori, 2011;Schulte-Merker, 2011;Witte et al, 2011). Transgenic mice have been created and markers for lymphatics have been identified that have made the study of lymphatic development much more accessible.…”