Lyve1

Recently, it has demonstrated that LYVE-1 receptor is a type I integral membrane polypeptide expressed on the cell surface as a 60 kDa protein, which is reduced to approximately 40 kDa by glycosidase treatment (27). LYVE-1 is abundant in spleen, lymph node, heart, lung, and fetal liver, less abundant in appendix, bone marrow, placenta, muscle, and adult liver, and absent in peripheral blood lymphocytes, thymus, brain, kidney, and pancreas. Expression of LYVE-1 is largely restricted to endothelial cells lining lymphatic vessels and splenic sinusoidal endothelial cells (27). LYVE-1 may be involved in hyaluronan metabolism in the lymphatic system (8, 28, 29). The co-localisation of LYVE-1 and hyaluronan on the luminal surface of lymphatic vessels suggests that HA may coat the lumen of lymphatic vessels through binding to LYVE-1 allowing hyaluronan-binding cells to adhere and migrate (27). The central core of the LYVE-1 Link module (C2-C3) is 57% identical to that of the human CD44 HA receptor, the only other Link superfamily HA receptor described to date with the closest homologue to LYVE-1. Nevertheless, there are distinct differences between LYVE-1 and CD44 suggesting that the two homologues differ either in the mode of HA binding or in its regulation. LYVE-1 receptor is almost exclusively restricted to lymph vessel endothelial cells, while CD44 is almost completely absent (27). While the highest concentration of LYVE-1 expression was found in submucosal lymph vessels underlying smooth muscle in the colon, and the lacteal vessels of intestinal villi that transport dietary lipid absorbed from the small intestine. CD44 is expressed abundantly in blood vessels and largely absent from lymphatic vessels (30). However, LYVE-1 is also expressed on sinusoidal endothelial cells of the spleen and placental syncytiotrophoblasts (8). The development of antibodies against LYVE-1 has made detection of lymphatics within tumours possible. For example, proliferating intra-tumoral lymph vessels have been identified in head and neck cancer (31). Studies on LYVE-1 as a lymphatic marker was also helped in detecting lymphatics in primary malignant melanoma (32). Furthermore, the presence of LYVE-1 in tumours can indeed promote lymph node metastasis.

Overexpression of VEGF-C in orthotopically transplanted MDA MB-435 or MCF-7 breast carcinoma (33, 34) or RIP 1/Tag2-RIP 1/VEGF-C transgenic mice (35), promoted proliferation of LYVE-1-positive lymph vessels and increased subsequent metastasis of tumour to lymph nodes.

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