Onkofetale Marker im hepatozellulären Karzinom
We are investigating the expression profile of Nope in the liver. This protein is localized in the plasma membrane of early hepatocytes and was initially identified in a microarray analysis where it showed a significantly higher expression level in purified hepatoblasts than in adult liver.
Projects actively being pursued
Neighbor of Punc E11 (Nope)
Expression profile in the liver
We were able to characterize Nope as an oncofetal surface marker in the liver. Currently, we are mainly focussed on its expression pattern in liver injury and liver regeneration in different mouse models.
Nope is a protein thought to be essential for axon guidance by similarity with its family members neogenin and deleted in colorectal cancer (Dcc). Neogenin is thought to act in netrin receptor-adhesive clustering and it may be involved in maintenance of multipotent progenitor cells since it is expressed during transition of undifferentiated into differentiated cell types. To find out more about the function of Nope, we are currently trying to establish a conditional Nope-/- mouse.
Human cancer tissue
We were able to establish Nope as a tumor marker for hepatocellular cancer in the mouse and more recently, we were able to identify Nope also in human hepatocellular cancer. Currently, we are working to identify Nope in various epithelial human cancer samples.
1) Bowe A, Zweerink S, Mück V, Kondylis V, Schulte S, Goeser T, Nierhoff D.
Depolarized Hepatocytes Express the Stem/Progenitor Cell Marker Neighbor of Punc E11 After Bile Duct Ligation in Mice. J Histochem Cytochem. 2018 Aug;66(8):563-576.
2) Gabriel E, Schievenbusch S, Kolossov E, Hengstler JG, Rotshteyn T, Bohlen H, Nierhoff D, Hescheler J, Drobinskaya I. Differentiation and selection of hepatocyte precursors in suspension spheroid culture of transgenic murine embryonic stem cells. PLoS One, 2012; 7(9):e44912. Epub 2012 Sep 24.
3) Schievenbusch S, Sauer E, Curth H-M, Schulte S, Demir M, Toex U, Goeser T and Nierhoff D. Neighbor of Punc E11 (Nope): Expression pattern of the new hepatic stem/progenitor cell marker during murine liver development. Stem Cells and Development, 2012, Sep 20; 21(14):2656-66.
4) Marquardt JU, Quasdorff M, Varnholt H, Curth HM, Mesghenna S, Protzer U, Goeser T, Nierhoff D. Neighbor of Punc E11, a novel onco-fetal marker for hepatocellular carcinoma.Int J Cancer, 2011, May 15; 128(10):2353-63.
5) Nierhoff D, LeVoci L, Schulte S, Goeser T, Rogler LE and Shafritz DA. New cell surface markers for murine fetal hepatic stem cells identified through high density complementary DNA microarrays. Hepatology, 2007, Aug; 46(2):535-47.
6) Gouon-Evans V, Boussemart L, Gadue P, Nierhoff D, Koehler CI, Kubo A, Shafritz DA, and Keller G. BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm. Nature Biotechnology, 2006, Nov; 24(11):1402-11.
7) Shafritz DA, Oertel M, Menthena A, Nierhoff D and Dabeva MA. Liver stem cells and prospects for liver reconstitution by transplanted cells. Hepatology, 2006, Feb; 43(2 Suppl 1):S89 – 98.
8) Ju W, Ogawa A, Heyer J, Nierhoff D, Liping Y, Kucherlapati R, Shafritz DA, and Boettinger EP. Deletion of Smad2 in mouse liver reveals novel functions in hepatocyte growth and differentiation. Molecular and Cellular Biology January, 2006, 26(2):654-667.
9) Nierhoff D, Ogawa A, Oertel M, Chen YC, Shafritz DA.Characterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity. Hepatology, 2005, Jul; 42(1):130-9.
10) Sachinidis A, Gissel C, Nierhoff D, Hippler-Altenburg R, Sauer H, Wartenberg M and Hescheler J.Identification of plateled-derived growth factor-BB as cardiogenesis-inducing factor in mouse embryonic stem cells under serum-free conditions. Cellular Physiology and Biochemistry, 2003, 13:423-429.
11) Nierhoff D, Horvath HC, Mytilineos J, Golling M, Bud O, Klar E, Opelz G, Voso MT, Ho AD, Haas R and Hohaus S.Microchimerism in bone marrow-derived CD34+ cells of patients after liver transplantation. Blood, 2000, July 15; 96(2): 763-767