LYVE1 explained

Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), also known as extracellular link domain containing 1 (XLKD1) is a Link domain-containing hyaladherin, a protein capable of binding to hyaluronic acid (HA), homologous to CD44, the main HA receptor.^[1] In humans it is encoded by the LYVE1 gene.^[2]

LYVE1 is a type I integral membrane glycoprotein. It acts as a receptor and binds to both soluble and immobilized hyaluronan. This protein may function in lymphatic hyaluronan transport and have a role in tumor metastasis.^[2] LYVE-1 is a cell surface receptor on lymphatic endothelial cells that can be used as a lymphatic endothelial cell marker, allowing for the isolation of these cells for experimental purposes. The physiological role for this receptor is still the subject of debate, but evolutionary conservation suggests an important role.

Expression of LYVE1 not restricted to lymph vessels but is also observed in normal liver blood sinusoids,^[3] and embryonic blood vessels.^[4]

LYVE1 expression is also observed in subset of macrophages.^{[5] [6]} LYVE1 positive macrophages in the meninges of rats are both lymphatic, as well as, alymphatic.^[7] In brain dura, the LYVE1+ macrophages were predominantly pleomorphic in morphology, while the cells in the spinal cord were pleomorphic in the cervical dura, while in the thoracal dura the cells were mainly round in morphology. The cells in brain dura were associated with collagen network in meninges, and some nonlymphatic LYVE1+ macrophages contained intracellular collagen. The exact function of these cells is yet unknown.

Further reading

• Jackson DG . The lymphatics revisited: new perspectives from the hyaluronan receptor LYVE-1 . Trends in Cardiovascular Medicine . 13 . 1 . 1–7 . January 2003 . 12554094 . 10.1016/S1050-1738(02)00189-5 .
• Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG . 6 . LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan . The Journal of Cell Biology . 144 . 4 . 789–801 . February 1999 . 10037799 . 2132933 . 10.1083/jcb.144.4.789 .
• Cunnick GH, Jiang WG, Gomez KF, Mansel RE . Lymphangiogenesis quantification using quantitative PCR and breast cancer as a model . Biochemical and Biophysical Research Communications . 288 . 4 . 1043–6 . November 2001 . 11689016 . 10.1006/bbrc.2001.5869 .
• Mouta Carreira C, Nasser SM, di Tomaso E, Padera TP, Boucher Y, Tomarev SI, Jain RK . LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis . Cancer Research . 61 . 22 . 8079–84 . November 2001 . 11719431 .
• Cursiefen C, Schlötzer-Schrehardt U, Küchle M, Sorokin L, Breiteneder-Geleff S, Alitalo K, Jackson D . Lymphatic vessels in vascularized human corneas: immunohistochemical investigation using LYVE-1 and podoplanin . Investigative Ophthalmology & Visual Science . 43 . 7 . 2127–35 . July 2002 . 12091407 .
• Huang SS, Tang FM, Huang YH, Liu IH, Hsu SC, Chen ST, Huang JS . Cloning, expression, characterization, and role in autocrine cell growth of cell surface retention sequence binding protein-1 . The Journal of Biological Chemistry . 278 . 44 . 43855–69 . October 2003 . 12912978 . 10.1074/jbc.M306411200 . free.
• Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T . 6 . Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries . DNA Research . 12 . 2 . 117–26 . 2007 . 16303743 . 10.1093/dnares/12.2.117 . free .
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD . Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry . Journal of Proteome Research . 4 . 6 . 2070–80 . 2006 . 16335952 . 1850943 . 10.1021/pr0502065 .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . 6 . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• Nguyen VA, Kutzner H, Fürhapter C, Tzankov A, Sepp N . Infantile hemangioma is a proliferation of LYVE-1-negative blood endothelial cells without lymphatic competence . Modern Pathology . 19 . 2 . 291–8 . February 2006 . 16424896 . 10.1038/modpathol.3800537 . free .
• Gu B, Alexander JS, Gu Y, Zhang Y, Lewis DF, Wang Y . Expression of lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) in the human placenta . Lymphatic Research and Biology . 4 . 1 . 11–7 . 2007 . 16569201 . 3072054 . 10.1089/lrb.2006.4.11 .
• Llovet JM, Chen Y, Wurmbach E, Roayaie S, Fiel MI, Schwartz M, Thung SN, Khitrov G, Zhang W, Villanueva A, Battiston C, Mazzaferro V, Bruix J, Waxman S, Friedman SL . 6 . A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis . Gastroenterology . 131 . 6 . 1758–67 . December 2006 . 17087938 . 10.1053/j.gastro.2006.09.014 . free .

Notes and References

1. Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG . 6 . LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan . The Journal of Cell Biology . 144 . 4 . 789–801 . February 1999 . 10037799 . 2132933 . 10.1083/jcb.144.4.789 .
2. Web site: LYVE1 lymphatic vessel endothelial hyaluronan receptor 1 [Homo sapiens (human) ]].
3. Mouta Carreira C, Nasser SM, di Tomaso E, Padera TP, Boucher Y, Tomarev SI, Jain RK . LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis . Cancer Research . 61 . 22 . 8079–84 . November 2001 . 11719431 .
4. Gordon EJ, Gale NW, Harvey NL . Expression of the hyaluronan receptor LYVE-1 is not restricted to the lymphatic vasculature; LYVE-1 is also expressed on embryonic blood vessels . Developmental Dynamics . 237 . 7 . 1901–9 . July 2008 . 18570254 . 10.1002/dvdy.21605 . 21324950 . free .
5. Lee HW, Qin YX, Kim YM, Park EY, Hwang JS, Huo GH, Yang CW, Kim WY, Kim J . 6 . Expression of lymphatic endothelium-specific hyaluronan receptor LYVE-1 in the developing mouse kidney . Cell and Tissue Research . 343 . 2 . 429–44 . February 2011 . 21181199 . 10.1007/s00441-010-1098-x . 1904976 .
6. Maruyama K, Asai J, Ii M, Thorne T, Losordo DW, D'Amore PA . Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing . The American Journal of Pathology . 170 . 4 . 1178–91 . April 2007 . 17392158 . 1829452 . 10.2353/ajpath.2007.060018 .
7. Brezovakova V, Jadhav S . Identification of Lyve-1 positive macrophages as resident cells in meninges of rats . The Journal of Comparative Neurology . January 2020 . 528 . 12 . 2021–2032 . 32003471 . 10.1002/cne.24870 . 210984721 .