title: Paralemmin-1 is expressed in lymphatic endothelial cells and modulates cell migration, cell maturation and tumor lymphangiogenesis.
abstract: The lymphatic system, the network of lymphatic vessels and lymphoid organs, maintains the body fluid balance and ensures the immunological surveillance of the body. In the adult organism, the de novo formation of lymphatic vessels is mainly observed in pathological conditions. In contrast to the molecular mechanisms governing the generation of the lymphatic vasculature during embryogenesis, the processes underlying pathological lymphangiogenesis are less well understood. A genome-wide screen comparing the transcriptome of tumor-derived lymphatic endothelial cells with that of blood vessel endothelial cells identified paralemmin-1 as a protein prominently expressed in lymphatic endothelial cells. Paralemmin-1 is a lipid-anchored membrane protein that in fibroblasts and neurons plays a role in the regulation of cell shape, plasma membrane dynamics and cell motility. Here, we show that paralemmin-1 is expressed in tumor-derived lymphatic endothelial cells as well as in lymphatic endothelial cells of normal, non-tumorigenic tissue. Paralemmin-1 represses cell migration and delays the formation of tube-like structures of lymphatic endothelial cells in vitro by modulating cell-substrate adhesion, filopodia formation and plasma membrane blebbing. While constitutive genetic ablation of paralemmin-1 expression in mice has no effect on the development and physiological function of the lymphatic system, the loss of paralemmin-1 impaired tumor-associated lymphangiogenesis. Together, these results newly identify paralemmin-1 as a protein highly expressed in lymphatic endothelial cells. Similar to its function in neurons, it may link the cytoskeleton to the plasma membrane and thereby modulate lymphatic endothelial cell adhesion, migration and lymphangiogenesis.
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland.
authors.forename: Imke
authors.initials: I
authors.lastname: Albrecht
authors.forename: Raphael
authors.initials: R
authors.lastname: Bieri
authors.forename: Angela
authors.initials: A
authors.lastname: Leu
authors.forename: Philipp
authors.initials: P
authors.lastname: Granacher
authors.forename: Jörg
authors.initials: J
authors.lastname: Hagmann
authors.forename: Manfred W
authors.initials: MW
authors.lastname: Kilimann
authors.forename: Gerhard
authors.initials: G
authors.lastname: Christofori
mesh_terms: D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000648:ultrastructure; D042783:Endothelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D007515:Islets of Langerhans / Q000378:metabolism; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000166:cytology* / Q000473:pathology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; C512641:Palm protein, mouse; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse