ABSTRACT
Antidepressants, which increase monoamine levels, induce glial cell line-derived neurotrophic factor (GDNF) release in C6 cells. Thus, we examined whether monoamines affect on GDNF release in C6 cells. We found that serotonin (5-HT) specifically increased GDNF mRNA expression and GDNF release in a dose- and time-dependent manner. The 5-HT-induced GDNF release was mediated through the MEK/mitogen-activated protein kinase (MAPK) pathway and, at least, 5-HT(2A) receptors. The action of 5-HT on GDNF release may provide important insights into the mechanism of antidepressants.
Subject(s)
Glioblastoma/metabolism , Nerve Growth Factors/metabolism , Serotonin/pharmacology , Animals , Cell Line, Tumor , Glial Cell Line-Derived Neurotrophic Factor , Nerve Growth Factors/biosynthesis , RatsABSTRACT
BACKGROUND: N-Acetylneuraminic acid and N-glycolylneuraminic acid (NeuGc) are the most common sialic acids in mammals, and NeuGc has attracted attention as a tumor-associated antigen. METHODS: In frozen liver sections from patients with hepatocellular carcinoma, glycolipid-type NeuGc was detected on the surface of liver cancer cells in 9 of 17 samples (52.9%) by immunostaining, using two chicken monoclonal antibodies against NeuGc and the tyramide signal amplification method. When conventional immunostaining without amplification was used, all 17 specimens tested were negative. RESULTS: Increased serum levels of anti-NeuGc IgG and/or IgM were observed in 13 of the 17 patients with hepatocellular carcinoma (76.5%). The presence of these antibodies was mostly attributed to the expression of NeuGc on hepatocellular carcinoma cells. Of the subjects with small HCCs (diameter 3 cm or less), 6 of 10 were positive for serum anti-NeuGc antibodies; however, 1 of these was negative for both serum Alpha-fetoprotein (AFP) and for prothrombin-induced vitamin K antagonist II (PIVKA-II). There was no correlation between serum AFP- or PIVKA-II, levels and the presence of NeuGc or anti-NeuGc IgG and/or IgM. CONCLUSION: The tyramide signal amplification method is useful for the immunohistochemical detection of low-level NeuGc expression by hepatocellular carcinoma cells. We therefore consider that measurement of serum levels of anti-NeuGc antibodies is clinically meaningful and that anti-NeuGc antibody may be a useful screening test, in combination with AFP and PIVKA-II, for the early diagnosis of hepatocellular carcinoma.
