Table 1.
Comparison of neuroendocrine mediators associated with cholangiocarcinoma (CCA).
| Mediator/Receptor | Upregulated/Downregulated in CCA | Promote/Inhibit CCA Growth | Note |
|---|---|---|---|
| Hormones | |||
| Sct/SR | Positive [24] | Inhibit [25] | Only limited numbers of CCA are positive to SR [24] |
| Somatostatin/SSTR2 | Positive [29] | Inhibit [29,30] | May not be effective in human CCA patients [31] |
| Melatonin/MT1 and MT2 | Downregulated [39] | Inhibit [39,40] | May also inhibit immune cell infiltration [42] |
| Estrogen/ER-α and ER-β | Upregulated [44] | Promote [46,47]/inhibit [55,56] | Different functions between ER-α and ER-β [46,47,55,56] |
| IGF-1 and IGF-2/IGF-1R and IGF-2R | Upregulated [46] | Promote [46] | Could be utilized as biomarkers [64,65] |
| Gastrin/CCK-BR | Upregulated [69] | Inhibit [70] | Calcium-dependent [70] |
| Neuropeptides | |||
| NGF-β/TrkA | Upregulated [73,76] | Promote [74,76] | May be limited in Asian patients [78] |
| SP/NK-1R | Upregulated [82] | Promote [82] | Lacking evidence in human CCA tumors |
| NPY/NPY receptors | Upregulated [87] | Inhibit [87] | Limited previous studies |
| Neurotransmitters | |||
| Dopamine/dopamine receptors | Upregulated [91] | Promote [91] | Limited previous studies |
| Serotonin/5-HT receptors | Upregulated [97] | Promote [97] | Functions may differ between receptors [95,96,97] |
| Histamine/histamine receptors | Upregulated [103] | Promote [103,104,105] inhibit [106,107] | Functions differ between H1/H2 and H3/H4 receptors [103,104,105,106,107] |