Morphogenesis, structure and properties of lymphatic vessels

Abstract

In this paper, we present literature results related to structure and various manners of lymphatic vessel formation during embryonic development and in pathological events, such as tumorigenesis, wound healing, and other diseases. The functions of the lymphatic system include the collection of fluids that enter tissues from the circulation, absorption of lipids and lipid-soluble vitamins from the intestine and their subsequent transport, participation in antigen, dendritic cell, and lymphocyte migration. The lymphatic system is also a route for tumor cell and inflammatory cell transport. Native lymphatic capillaries differ from blood capillaries by having an irregular lumen, a discontinuous basement membrane, absence of pericytes, and a strong anchorage of their endothelial cells to the extracellular matrix via microfibrils built of emilin and fibrillin. Lymphatic endothelial cells express surface antigens such as Lyve-1, podoplanin, VEGFR3 (Flk4) and transcription factor Prox-1, as well as molecules which are common for blood endothelial cells and lymphatic endothelial cells (CD31, CD34, Flk-1, Tie-1, Tie-2, neuropilin 2). Lymphatic vessel formation during embryonic development starts with the occurrence of lymphatic sacs sprouting from systemic jugular veins and/or by co-option of lymphangioblasts or hematopoietic-derived cells. It can also proceed by dedifferentiation of venous endothelial cells after their detachment from the venous system, migration to the target places within the body and assembly in the lymphatic lumen. Mechanisms of lymphatic vessel formation during embryonic development and in pathological conditions, such as tumorigenesis, wound healing, and metastasis, is regulated by a plethora of growth factors and molecules, among which the most important are VEGF-C, VEGF-D, HGF, FGF, retinoic acid, IL-3, and IL-7. Macrophages and cells bearing CD45 phenotype seem to take part in the formation of lymphatics. Macrophages might act as a source of growth factors and/or as modulators playing a role in vessel caliber regulation during lymphangiogenesis. We discuss the most important diseases of the lymphatic system, their molecular basis and tumors derived from lymphatic vessels.

Characteristics of the Colorectal Cancer Microenvironment—Role in Cancer Progression and Therapeutic Possibilities

“…These cells build transport pathways that maintain homeostasis in physiological processes by regulating vessel permeability and tension. However, their primary functions can be exploited by tumors for survival and invasion [214][215][216]. Tumor progression involves proliferation and the growth of the tumor mass.…”

Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity

“…From the primary lymphoid organs, lymphocytes enter the secondary lymphoid organs, or the spleen, lymph nodes, mucosa-associated lymphoid tissue (MALT), bronchus-associated lymphoid tissue (BALT) and gut-associated lymphoid tissue (GALT), where the cells of the immune system proliferate and mature [ 80 , 81 ]. On the other hand, the lymphatic vessel system is a unidirectional network which, based on the function as well as the size of the vessels, is divided into four parts [ 82 , 83 ]. Lymphatic capillaries, as the initial vessels, consist of a single LEC layer, connected directly to the interstitial tissue by “anchoring” in the surrounding connective tissue by means of fine filaments made of emilin and fibrillin [ 84 , 85 ].…”