Table 1.

Studies documenting altered opioid receptor expression in cancer.

Receptor	Cancer	Sample	Mode of Detection	Findings	Result	Reference
μ-opioid receptor	Metastatic Lung Cancer	Tissue samples	Immunohistochemistry	μOR expression was increased significantly in cancer samples from patients with lung cancer compared with adjacent control tissue	μOR ↑	Singleton (18)
μ-opioid receptor	Laryngeal Carcinoma	Tissue samples	Immunohistochemistry	μOR staining intensity was significantly increased in laryngeal-carcinoma compared to the adjacent normal tissue	μOR ↑	Lahav (19)
μ-opioid receptor	Laryngeal squamous cell carcinoma (LSCC)	Tissue samples	Immunohistochemistry	μOR levels in tumour tissues were significantly higher than those in adjacent non-tumour tissue There was a statistically significant relationship between high μOR and low disease-free survival	μOR ↑	Zhang (20)
μ-opioid receptor	Lung Cancer	Murine Lewis Lung Carcinoma (LLC) cells, various human non-small cell lung cancer (NSCLC) cells and non-tumorigenic human BEAS-2B cells	Immunohistochemistry	μOR expression levels were higher in bronchioloalveolar carcinoma, adenocarcinoma and, to a lesser extent, squamous cell carcinoma than in normal lung samples	μOR ↑	Matthew (21)
μ-opioid receptor	Prostate Cancer	Tumour specimens from 113 patients with Stage IV prostate cancer and samples of benign prostatic hyperplasia (BPH) used as controls	Laser scanning confocal microscopy. Images were processed to quantitate μOR-ir as a marker of μOR expression	Tumour samples had a greater μOR expression than BPH control samples. In samples with high μOR expression, the receptor was generally localised to the membrane, whereas in samples with low expression it was internalised (perhaps inactive)	μOR ↑	Zylla (22)
μ-opioid receptor	Stage I-III Pancreatic Ductal Adenocarcinoma	Tissue Samples	Immunohistochemistry	There was no significant differences between μOR expression levels in the tumour and adjacent non-tumour tissues	–	Zhang (23)
μ and κ-opioid receptors	Breast cancer	Tissue samples	Immunohistochemistry	No difference in μOR or κOR between primary tumour, peritumoral area and lymph node metastasis Significantly less κOR in lymph node samples from patient with recurrence vs patients with no recurrence	–	De Sousa (24)
δ–opioid receptor	Lung Cancer	SCLC cell lines (SCLC-22H and 16HC) and NSCLC cell line (NCI-23)	RT-PCR binding assay and DNA sequence analysis	mRNA expression of δ–OR detected in all five SCLC but low level in NSCLC cell line and none in in normal lung tissue or cultured lung fibroblasts DNA seq. analysis of SCLC-22H, 16HC and NCI-23 revealed that the δOR was not mutated	δOR ↑	Schreiber (25)
δ–opioid receptor	Breast cancer	Cultured cells, (cancer: MCF-7, MDA-MB-231, SKBR-3 and epithelial MCF-10F) Patient tissue sections	RT-PCR Western blot	δOR mRNA and protein expression was significantly higher in breast cancer tissues than in the corresponding paracancerous tissues δOR expression was positively correlated with tumour metastasis, clinical stage, and poor prognosis	δOR ↑	Wei (26)
δ–opioid receptor	Hepatocellular Carcinoma	Cultured cells (LO2, HepG2, and Hep3B) and tissue sections	RT-PCR Western blot Immunohistochemistry	δOR mRNA and protein levels higher in HCC lesions than in the adjacent tissues and normal liver tissues Results also indicate that activation of δOR promotes HCC cell proliferation	δOR ↑	Tang (27)
δ-opioid receptors	Lung cancer	SCLC and NSCLC cell lines, normal mouse lung membranes	Radiolabelled δ-opioid receptor ligand binding	6 SCLC but not NSCLC cell lines or normal mouse lung membranes showed δ-opioid receptor binding (specifically of the δ2 subtype)	δOR ↑	Campa (28)
μ and δ-opioid receptors	Lung Cancer	Human cancer patients, in vivo imaging	PET analysis of kinetics and distribution of binding of δOR- and μOR- binding tracers C-MeNTI and C-CFN	μOR and δOR were significantly μOR e abundant in lung carcinoma than in the normal host tissue Relative increase in δOR in malignant lesions is greater than that of the μOR	μOR ↑ δOR ↑	Madar (29)
μ, δ, and κ-opioid receptors	Stage I-III Triple Negative Breast Cancer	Publicly available bulk RNA-seq data	RNA-seq analysis of tissue or single cells	μOR expression extremely low in both cancer and normal tissue κOR, δOR and OGFR expression higher in tumour vs normal tissue κOR mostly on cancer cells, OGFR mostly on immune cells	δOR ↑ κOR ↑	Montagna (30)
μ, δ, and κ-opioid receptors	Oesophageal Squamous Cell Carcinoma (ESCC)	Cultured cells and tissue sections	Flow cytometry Immunocytochemistry Western blot Immunohistochemistry	All OR receptors expressed in ESCC cell lines, to varying degree κOR membrane, cytoplasmic and nuclear localisation detected κOR expression increases with tumour grade. Nuclear κOR correlates with lymph node metastasis and poor prognosis	κOR ↑	Zhang (31)
Opioid Growth Factor receptor (OGFr)	Pancreatic and colon cancer	Human PaCa-2, BxPC-3, Capan-2 (pancreatic) HT-29, HCT 116 (colon) inoculated into nude mice	Receptor binding analysis Northern blot	No differences in receptor binding or gene expression between cancer cells in vitro and small, medium, or large tumours	–	Zagon (32)