Table 2.
Neuropeptides involving in tumour development through cAMP related pathways (↑ refers to up-regulation, ↓ refers to down-regulation).
| Cancer Type | Neuropeptides | Receptor (s) | Cell Line/Model (s) | Downstream Pathway (s) | Function (s) | Reference (s) |
|---|---|---|---|---|---|---|
| Breast cancer | NPY | Y1R | MCT-7, 4T1 | −cAMP | ↓ Cell proliferation | [84,85] |
| Y5R | BT-549, 4T1, primary breast neoplasia tissue | +MAPK and ERK1/2 | ↑ Cell proliferation ↑ Metastasis |
[86,87,88] | ||
| PYY | Y4R | MCT-7 | −cAMP | ↓ Cell proliferation | [89,90,91] | |
| VIP | VPAC1, VPAC2 | Cancer stem cells from MCT-7 | +cAMP/PKA | ↑ Tumour growth ↓ Apoptosis |
[92] | |
| GnRH | GnRHR | MCT-7, MDA-MB-231 | +cAMP/PKA | ↓ Cell proliferation ↑ Apoptosis ↓ Invasiveness |
[93,94,95,96] | |
| Endometrial Adenocarcinoma | OT | OTR | Colo 684, A-MEC, HEC1A, and Ishikawa cells, human endometrial neoplasm tissues | +cAMP/PKA | ↓ Cell proliferation | [97,98] |
| Glioblastoma (GBM) |
VIP/PACAP | PAC1 receptor, VPAC1 and VPAC2 | M059J, M059K, U87 | +AKT (in M059K cells) +AKT via PKA, Rac1, Cdc42 |
↓ Invasiveness | [99] |
| Leukemia | VIP | VPAC1 and VPAC2 | human erythroleukaemia (HEL) | +AC and PLC | ↓ Cell proliferation | [100] |
| PACAP | PAC1, VPAC1 and VPAC2 | human myeloid leukaemia | +Ca2+ level | ↓ Cell proliferation | ||
| SST analog (Octreotide) | SSTR | Jurkat cells | +AC | ↓ Cell proliferation | [101] | |
| Small cell lung cancer (SCLC) | VIP | VPAC1 | SCLC, SCLC patients samples | +AC | ↑ Cell proliferation (Low doses) | [102] |
| ↓ Cell proliferation (High doses) | ||||||
| Non-small-cell lung cancer (NSCLC) | VIP | VPAC1 | NSCLC, NSCLC patient samples | +AC | ↑ Cell proliferation (Low doses) | [102] |
| ↓ Cell proliferation (High doses) | ||||||
| Neuroblastoma | OT | OTR | SK-N-SH, SH-SY5Y, IMR-32 and MOG-G-UVW | +cAMP | ↓ Cell proliferation | [103] |
| Ovarian cancer | NPY | Y1R, Y2R | Human ovarian tissue | −AC −cAMP levels |
↑ Cell proliferation ↑ Angiogensis |
[104,105] |
| Prostate cancer | NPY | Y1R | PCa cell lines (LNCaP, DU145, PC3) | +ERK1/2 (in DU145 cells) −cAMP, + ERK1/2 via PKC (in PC3 cells) |
↓ Cell proliferation (in LNCaP, DU145 cells) ↑ Cell proliferation (in PC3 cells) |
[106,107] |
| VIP | VPAC1 | LNCaP, PC3, PC3 nude mice xenograft | +PKA | ↑ Tumour growth | [108,109] | |
| CT | CTR | PC-3M, LNCaP and PC-3 | +cAMP and Ca2+ | ↑ Cell proliferation ↑ Invasiveness |
[110,111,112] | |
| AM | AMR, CLR, RAMP2 and RAMP3 | LNCaP, DU145 and PC-3, xenografts model | +cAMP and CRAF/MEK/ERK | ↑ Cell proliferation ↑ Invasiveness |
[113,114] | |
| GnRH | GnRHR | LNCaP, DU145, and BPH-1 | −cAMP | ↓ Cell proliferation | [115,116,117,118,119,120] | |
| Renal cell carcinoma (RCC) | AVP | VR | 786-O and Caki-1 cells, mouse xenografts | +cAMP +ERK1/2 |
↑ Cell proliferation | [121] |