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Biogenic amines secreted by cholangiocarcinoma modulate macrophage activation
Author(s) -
LeyvaIllades Dinorah,
DeMorrow Sharon
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.387.8
Subject(s) - serotonin , flow cytometry , cancer research , macrophage , tumor microenvironment , cd68 , chemistry , dopamine , secretion , biology , medicine , microbiology and biotechnology , endocrinology , immunology , immunohistochemistry , biochemistry , in vitro , receptor , tumor cells
Cholangiocarcinoma (CCA) arise from the neoplastic transformation of epithelial cells that line bile ducts. In addition to neoplastic cells, the tumor microenvironment consists of inflammatory cells and fibroblasts, which support tumor growth. Most tumor‐associated macrophages (TAMs) have an M2‐like anti‐tumor phenotype. How TAMs are involved in CCA progression remains unclear. CCA cells secrete increased amounts of serotonin and dopamine leading to increased proliferation; however, additional consequences of this secretion remain to be studied. The aim of this study was to determine the effects of serotonin and dopamine on macrophage activation. Macrophages were found in both benign and CCA tumors as evidenced by CD68 immunoreactivity, while IL‐10 (marker of M2 macrophages) was only found in CCA tissue. IFNγ increased cell surface MHCII expression measured by flow cytometry whereas pretreatment with CCA conditioned media (CM), serotonin, or dopamine dampened MHCII expression. CIITA mRNA expression (major regulator of MHCII expression) increased after IFNγ treatment which was dampened with CCA CM or serotonin. Treatment with CCA CM, serotonin or dopamine inhibited the nuclear translocation of Stat1 without altering the phosphorylation status. These data suggest that biogenic amines may play a role in the phenotypic switch from M1 to M2 of TAMs in the CCA tumor microenvironment.