No information exists on the role of neuropeptide Y (NPY) in cholangiocarcinoma growth. Therefore, we evaluated the expression and secretion of NPY and its subsequent effects on cholangiocarcinoma growth and invasion. Cholangiocarcinoma cell lines and nonmalignant cholangiocytes were used to assess NPY mRNA expression and protein secretion. NPY expression was assessed by immunohistochemistry in human liver biopsies. Cell proliferation and migration were evaluated in vitro by MTS assays and matrigel invasion chambers, respectively, after treatment with NPY or a neutralizing NPY antibody. The effect of NPY or NPY depletion on tumor growth was assessed in vivo after treatment with NPY or the neutralizing NPY antibody in a xenograft model of cholangiocarcinoma. NPY secretion was upregulated in cholangiocarcinoma compared with normal cholangiocytes. Administration of exogenous NPY decreased proliferation and cell invasion in all cholangiocarcinoma cell lines studied and reduced tumor cell growth in vivo. In vitro, the effects of NPY on proliferation were blocked by specific inhibitors for NPY receptor Y2, but not Y1 or Y5, and were associated with an increase in intracellular D-myo-inositol 1,4,5- trisphosphate and PKCα activation. Blocking of NPY activity using a neutralizing antibody promoted cholangiocarcinoma growth in vitro and in vivo and increased the invasiveness of cholangiocarcinoma in vitro. Increased NPY immunoreactivity in human tumor tissue occurred predominantly in the center of the tumor, with less expression toward the invasion front of the tumor. We demonstrated that NPY expression is upregulated in cholangiocarcinoma, which exerts local control on tumor cell proliferation and invasion. Modulation of NPY secretion may be important for the management of cholangiocarcinoma

Demorrow, S., Onori, P., Venter, J., Invernizzi, P., Frampton, G., White, M., et al. (2011). Neuropeptide Y inhibits cholangiocarcinoma cell growth and invasion. AMERICAN JOURNAL OF PHYSIOLOGY. CELL PHYSIOLOGY, 300(5), C1078-C1089 [10.1152/ajpcell.00358.2010].

Neuropeptide Y inhibits cholangiocarcinoma cell growth and invasion

INVERNIZZI, PIETRO;Bernuzzi, Francesca Veronica;
2011

Abstract

No information exists on the role of neuropeptide Y (NPY) in cholangiocarcinoma growth. Therefore, we evaluated the expression and secretion of NPY and its subsequent effects on cholangiocarcinoma growth and invasion. Cholangiocarcinoma cell lines and nonmalignant cholangiocytes were used to assess NPY mRNA expression and protein secretion. NPY expression was assessed by immunohistochemistry in human liver biopsies. Cell proliferation and migration were evaluated in vitro by MTS assays and matrigel invasion chambers, respectively, after treatment with NPY or a neutralizing NPY antibody. The effect of NPY or NPY depletion on tumor growth was assessed in vivo after treatment with NPY or the neutralizing NPY antibody in a xenograft model of cholangiocarcinoma. NPY secretion was upregulated in cholangiocarcinoma compared with normal cholangiocytes. Administration of exogenous NPY decreased proliferation and cell invasion in all cholangiocarcinoma cell lines studied and reduced tumor cell growth in vivo. In vitro, the effects of NPY on proliferation were blocked by specific inhibitors for NPY receptor Y2, but not Y1 or Y5, and were associated with an increase in intracellular D-myo-inositol 1,4,5- trisphosphate and PKCα activation. Blocking of NPY activity using a neutralizing antibody promoted cholangiocarcinoma growth in vitro and in vivo and increased the invasiveness of cholangiocarcinoma in vitro. Increased NPY immunoreactivity in human tumor tissue occurred predominantly in the center of the tumor, with less expression toward the invasion front of the tumor. We demonstrated that NPY expression is upregulated in cholangiocarcinoma, which exerts local control on tumor cell proliferation and invasion. Modulation of NPY secretion may be important for the management of cholangiocarcinoma
Articolo in rivista - Articolo scientifico
Cholangiocyte; Microenvironment; Migration; Protein kinase C; Animals; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cholangiocarcinoma; Humans; Inositol 1,4,5-Trisphosphate; Mice; Mice, Nude; Neoplasm Invasiveness; Neuropeptide Y; Protein Kinase C; Receptors, Neuropeptide Y; Cell Biology; Physiology
English
C1078
C1089
Demorrow, S., Onori, P., Venter, J., Invernizzi, P., Frampton, G., White, M., et al. (2011). Neuropeptide Y inhibits cholangiocarcinoma cell growth and invasion. AMERICAN JOURNAL OF PHYSIOLOGY. CELL PHYSIOLOGY, 300(5), C1078-C1089 [10.1152/ajpcell.00358.2010].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/106418
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