Lymphangiogenic factors, mechanisms, and applications
Wei Zheng, … , Aleksanteri Aspelund, Kari Alitalo
Wei Zheng, … , Aleksanteri Aspelund, Kari Alitalo
Published March 3, 2014
Citation Information: J Clin Invest. 2014;124(3):878-887. https://doi.org/10.1172/JCI71603.
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Review Series

Lymphangiogenic factors, mechanisms, and applications

Abstract

Lymphangiogenesis, the growth of lymphatic vessels, is essential in embryonic development. In adults, it is involved in many pathological processes such as lymphedema, inflammatory diseases, and tumor metastasis. Advances during the past decade have dramatically increased the knowledge of the mechanisms of lymphangiogenesis, including the roles of transcription factors, lymphangiogenic growth factors and their receptors, and intercellular and intracellular signaling cascades. Strategies based on these mechanisms are being tested in the treatment of various human diseases such as cancer, lymphedema, and tissue allograft rejection. This Review summarizes the recent progress on lymphangiogenic mechanisms and their applications in disease treatment.

Authors

Wei Zheng, Aleksanteri Aspelund, Kari Alitalo

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Figure 1

Growth factor and cytokine signaling pathways in lymphangiogenesis.

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Growth factor and cytokine signaling pathways in lymphangiogenesis. Grow...
Growth factors derived from tumor cells, inflammatory cells, or other cell types activate their receptors on the surface of LECs and initiate various signaling cascades, leading to lymphatic vessel growth. Coordinately, these factors regulate cell migration, proliferation, and survival and vessel dilation and remodeling. Interactions between adjacent LECs via ANG/TIE2, DLL4/Notch1, and EFNB2/EPHB4 also contribute to the regulation of lymphangiogenic activity. Note that in contrast to ANG1, ANG2 is predominantly an autocrine ligand and that both angiopoietins bind with equal affinity to TIE2 and induce in trans ligand receptor complexes among ECs (103). Inhibitors that target the various involved molecules are indicated in red, and some of the key signaling consequences in blue.