Lymphangiogenesis Guidance by Paracrine and Pericellular Factors
Downloaded from genesdev.cshlp.org on October 10, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Lymphangiogenesis guidance by paracrine and pericellular factors Kari Vaahtomeri,1 Sinem Karaman,1 Taija Mäkinen,2 and Kari Alitalo1 1Wihuri Research Institute, Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, FI-00014 Helsinki, Finland; 2Department of Immunology, Genetics, and Pathology, Uppsala University, 75185 Uppsala, Sweden Lymphatic vessels are important for tissue fluid homeo- in the downstream collector vessels (Bazigou and Maki- stasis, lipid absorption, and immune cell trafficking and nen 2013). are involved in the pathogenesis of several human diseas- With the exception of the Schlemm’s canal in the eyes, es. The mechanisms by which the lymphatic vasculature meningeal lymphatic vessels, and the majority of the (lac- network is formed, remodeled, and adapted to physiolog- teal) lymphatic vessels in the intestine, most lymphatic ical and pathological challenges are controlled by an intri- networks are generated during embryonic development cate balance of growth factor and biomechanical cues. (Kim et al. 2007; Aspelund et al. 2014, 2015; Kizhatil These transduce signals for the readjustment of gene ex- et al. 2014; Nurmi et al. 2015). However, they also under- pression and lymphatic endothelial migration, prolifera- go dynamic changes in adults. Lymphatic vessels can tion, and differentiation. In this review, we describe grow in length and caliber (lymphangiogenesis) in various several of these cues and how they are integrated for the pathological conditions, such as inflammation, wound generation of functional lymphatic vessel networks. healing, tumorigenesis, and in association with tissue transplantation. A common feature in many of these con- ditions is tissue edema and inflammation, which increase Some of the most dense lymphatic networks are located the demand for fluid drainage and immune cell traffick- under various epithelia that form the interface between ing.
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