|Neurotransmitters||Receptor||Type of cancer||Model||Mechanism/pathway||Ref.|
|NE||β2-AR||Pancreatic cancer||CFPAC1, MiaPaCa2 Panc1, and IMIM-PC2 cells||NE treatment reduces migratory activity of pancreatic cancer cells. NE mediates inhibitory effect via imbalanced activation of PKC/PLC signaling pathway → to activation of anti-migratory cAMP/PKA signalling.|||
|Prostate cancer||Subcutaneous injection of PC-3 cells in BALB/c nude mice||↑ NE leads to lumbar lymph node metastasis in an animal model.||[156, 157]|
|DA||DR1 & DR5||HCC||
Tumor and non-tumor adjacent tissues from patients; LM3, Huh7 and SNU449 cells;|
subcutaneous injection of LM3 cells in BALB/c nude mice
DR5 is upregulated in tumor tissue and DR1 is upregulated in non-tumor human tissues.|
Dopamine ↑ cell proliferation in SNU449 cells.
Administration of DR antagonist (thioridazine) inhibits cell proliferation in vitro and in and cell migration through EMT → ↓ tumor metastasis
|GABA||GABAA||HCC||Human primary and adjacent non-tumor tissues, and Orthotopic inoculation of SMMC-7721 cells into the liver of BALB/c nude mice||
GABAAreceptor subunit ε1 expression is lower in human HCC tissues than in non-tumor liver tissues.|
GABA inhibits invasion and migration of human liver cancer cells in vitro.
In mice, inoculation of SMMC-7721 cells pretreated with GABA ↓ tumor metastasis.
|GABAB||PLC/PRF/5 and Huh cells||Administration of GABAB agonist (baclofen) ↓ cell migration associated with ↓ in intracellular cAMP levels.|||
|Breast cancer||Human tissues, 4 T1 and MCF-7 cells||Administration of GABAB agonist (baclofen) promotes invasion and migration of breast cancer cells in vitro and metastasis in vivo via ERK1/2 and MMP-2signaling pathway.|||
|Prostate cancer||Human prostate and lymph node tissues, C4–2 cells||↑ Expression of GABA → cell invasion in vitro and lymph node metastasis in patients mediated by activation of MMPs signalling.|||
|HCC||Human primary and adjacent non-tumor tissues||The mRNA levels of GABAB R1.2 and GABAB R1.4 are higher in HCC tissues than in non-tumor liver tissues|||
|ACh||AR||HCC||SNU-449 cells||ACh activates AR receptors → ↑ invasion and migration of SNU-449 cells via activation of AKT and STAT3 signaling pathways.|||
|α7-nAChR||Pancreatic cancer||CD18/HPAF, Capan1, FG/Colo357 cells in vitro and orthotopically implanted CD18/HPAF cells in immunodeficient mice||
Nicotine treatment stimulates the expression of α7-nAChR and MUC4 in vitro. In the in vivo model, exposure to low and high cigarette smoking increases the tumor metastasis and MUC4 expression compared to sham controls.|
Nicotine induces tumor metastasis by upregulating MUC4 via α7-nAChR-mediated JAK2/STAT3 signaling in collaboration with Ras/Raf/MEK/ERK1/2 signalling pathway.
|Lung cancer||Line 1 cells in vitro, and subcutaneous injection of Line 1 cells in BALB/c mice||Intraperitoneal injection of nicotine ↑ tumor growth and metastasis through change in gene expression via nAChR signalling pathway.|||
|nAChR β2||Lung cancer||B16 cells intravenous injection in C57BL/6 mice||↑ Nicotine exposure → activation of nAChR β2 on NK cells mediates metastasis|||
|α9-nAChR||Breast cancer||MDA-MB-231 and MCF-7 cells||Nicotine treatment enhances the migratory abilities of both cells by activating α9-nAChR through elevated expression of EMT markers|||
|mAChR||Colon cancer||Hh508 and SNU-C4 cells||
Administration of muscarinic inhibitor (atropine) → ↓ cell invasion and migration.|
ACh binding to M3R mediates cell migration via the activation of post-ERBB1, ERK and PI3K-dependent RhoA pathway.
|NSCLC||Human tissues, micA549, PC9, SPC-A1, GLC82, L78 and HLF cells||
M3R expression correlates with clinical stage and poor survival in patients.|
M3R stimulation by ACh enhances in vitro cell invasion and migration via PI3K/AKt pathway.
Hi-Myc transgenic mice-bearing PC-3
Presences of cholinergic nerve fibers associate with poor clinical outcome in human patients.|
Pharmacological blockade or genetic disruption of the M1R inhibit metastasis leading to improved survival of the mice
|SP||NK-1R||Pancreatic cancer||MiaPaCa-2, BxPC-3, CFPAC-1, HAPC, Panc-1, and SW1990 cells||Binding of SP to NK-1R promotes cell invasion and migratory potential which is mediated by expression of MMP-2. SP also increases cell migration and neurite outgrowth toward DRG demonstrating important role in metastasis and PNI.||[146, 161]|
SCID/beige mice bearing SK-ES1 cells
Enhanced level of systemic NPY associate with metastatic tumors.|
In the xenograft model, NPY expression associate with bone metastases.
|Y5||Breast cancer||4 T1 cell line||NPY mediates metastatic effect via the activation of Y5 receptor.|||
|Neurotensin||NTSR1||Breast cancer||Human tissues||The expression of NTSR1 associates with lymph node metastasis.|||