Current Status of Lymphangiogenesis: Molecular Mechanism, Immune Tolerance, and Application Prospect

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Feb 25

PMID 36831512

Authors

Hongyang Deng

Jiaxing Zhang

Fahong Wu

Fengxian Wei

Wei Han

Xiaodong Xu

Youcheng Zhang

Affiliations

Soon will be listed here.

Abstract

The lymphatic system is a channel for fluid transport and cell migration, but it has always been controversial in promoting and suppressing cancer. VEGFC/VEGFR3 signaling has long been recognized as a major molecular driver of lymphangiogenesis. However, many studies have shown that the neural network of lymphatic signaling is complex. Lymphatic vessels have been found to play an essential role in the immune regulation of tumor metastasis and cardiac repair. This review describes the effects of lipid metabolism, extracellular vesicles, and flow shear forces on lymphangiogenesis. Moreover, the pro-tumor immune tolerance function of lymphatic vessels is discussed, and the tasks of meningeal lymphatic vessels and cardiac lymphatic vessels in diseases are further discussed. Finally, the value of conversion therapy targeting the lymphatic system is introduced from the perspective of immunotherapy and pro-lymphatic biomaterials for lymphangiogenesis.

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References

Ducoli L, Detmar M . Beyond PROX1: transcriptional, epigenetic, and noncoding RNA regulation of lymphatic identity and function. Dev Cell. 2021; 56(4):406-426. DOI: 10.1016/j.devcel.2021.01.018. View

Chen C, Zheng H, Luo Y, Kong Y, An M, Li Y . SUMOylation promotes extracellular vesicle-mediated transmission of lncRNA ELNAT1 and lymph node metastasis in bladder cancer. J Clin Invest. 2021; 131(8). PMC: 8262506. DOI: 10.1172/JCI146431. View

Riabov V, Gudima A, Wang N, Mickley A, Orekhov A, Kzhyshkowska J . Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front Physiol. 2014; 5:75. PMC: 3942647. DOI: 10.3389/fphys.2014.00075. View

Soriente A, Amodio S, Fasolino I, Raucci M, Demitri C, Engel E . Chitosan/PEGDA based scaffolds as bioinspired materials to control in vitro angiogenesis. Mater Sci Eng C Mater Biol Appl. 2020; 118:111420. DOI: 10.1016/j.msec.2020.111420. View

Louveau A, Herz J, Alme M, Salvador A, Dong M, Viar K . CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018; 21(10):1380-1391. PMC: 6214619. DOI: 10.1038/s41593-018-0227-9. View

Karaman S, Detmar M . Mechanisms of lymphatic metastasis. J Clin Invest. 2014; 124(3):922-8. PMC: 3938272. DOI: 10.1172/JCI71606. View

Baik J, Park H, Kataru R, Savetsky I, Ly C, Shin J . TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation. Clin Transl Med. 2022; 12(6):e758. PMC: 9160979. DOI: 10.1002/ctm2.758. View

Li W, Hsiao K, Wang C, Chang N, Hsu P, Sun C . Extracellular vesicle-associated VEGF-C promotes lymphangiogenesis and immune cells infiltration in endometriosis. Proc Natl Acad Sci U S A. 2020; 117(41):25859-25868. PMC: 7568311. DOI: 10.1073/pnas.1920037117. View

Clavin N, Avraham T, Fernandez J, Daluvoy S, Soares M, Chaudhry A . TGF-beta1 is a negative regulator of lymphatic regeneration during wound repair. Am J Physiol Heart Circ Physiol. 2008; 295(5):H2113-27. DOI: 10.1152/ajpheart.00879.2008. View

10.

Baeyens A, Schwab S . Finding a Way Out: S1P Signaling and Immune Cell Migration. Annu Rev Immunol. 2020; 38:759-784. DOI: 10.1146/annurev-immunol-081519-083952. View

11.

Alderfer L, Wei A, Hanjaya-Putra D . Lymphatic Tissue Engineering and Regeneration. J Biol Eng. 2018; 12:32. PMC: 6296077. DOI: 10.1186/s13036-018-0122-7. View

12.

Chen J, Wang L, Xu H, Xing L, Zhuang Z, Zheng Y . Meningeal lymphatics clear erythrocytes that arise from subarachnoid hemorrhage. Nat Commun. 2020; 11(1):3159. PMC: 7308412. DOI: 10.1038/s41467-020-16851-z. View

13.

Hsu M, Rayasam A, Kijak J, Choi Y, Harding J, Marcus S . Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells. Nat Commun. 2019; 10(1):229. PMC: 6335416. DOI: 10.1038/s41467-018-08163-0. View

14.

Lin T, Zhang X, Lu Y, Gong L . TGFBIp mediates lymphatic sprouting in corneal lymphangiogenesis. J Cell Mol Med. 2019; 23(11):7602-7616. PMC: 6815832. DOI: 10.1111/jcmm.14633. View

15.

Mece O, Houbaert D, Sassano M, Durre T, Maes H, Schaaf M . Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis. Nat Commun. 2022; 13(1):2760. PMC: 9120506. DOI: 10.1038/s41467-022-30490-6. View

16.

Nakamoto S, Ito Y, Nishizawa N, Goto T, Kojo K, Kumamoto Y . Lymphangiogenesis and accumulation of reparative macrophages contribute to liver repair after hepatic ischemia-reperfusion injury. Angiogenesis. 2020; 23(3):395-410. DOI: 10.1007/s10456-020-09718-w. View

17.

Rinderknecht M, Detmar M . Tumor lymphangiogenesis and melanoma metastasis. J Cell Physiol. 2008; 216(2):347-54. DOI: 10.1002/jcp.21494. View

18.

Xiong Y, Hla T . S1P control of endothelial integrity. Curr Top Microbiol Immunol. 2014; 378:85-105. PMC: 4240614. DOI: 10.1007/978-3-319-05879-5_4. View

19.

Tantari M, Bogliolo S, Morotti M, Balaya V, Bouttitie F, Buenerd A . Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study. Cancers (Basel). 2022; 14(1). PMC: 8750515. DOI: 10.3390/cancers14010212. View

20.

McDonald B, Kubes P . Interactions between CD44 and Hyaluronan in Leukocyte Trafficking. Front Immunol. 2015; 6:68. PMC: 4330908. DOI: 10.3389/fimmu.2015.00068. View