MOR1 Expression in Gastric Cancer: A Biomarker Associated With Poor Outcome

Yao, M M Ya-sai; Yao, Ruyong; Zhuang, Likun; Qi, Weiwei; Lv, Mengying; Zhou, Fei; Qiu, Miao Zhen; Yue, Lu

doi:10.1111/cts.12246

Cited by 33 publications

(29 citation statements)

References 34 publications

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“…The mu-opioid receptor (MOR) has been shown to be widely distributed in limbic and cortical regions such as the NAcc 18,19 . Therefore, we wanted to first demonstrate the presence of MOR in NAcc neurons of the mouse by targeting the most common MOR isoform, MOR1 20 . The anti-MOR1 antibody conjugated with FITC was used in conjunction with DAPI nuclear stain.…”

Section: Colocalization Of Gad67 and Mor1 In Mouse Naccmentioning

confidence: 99%

Colocalization of MOR1 and GAD67 in Mouse Nucleus Accumbens

Hinkle

Dedkov

Buono

et al. 2019

Preprint

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Current understanding of the rewarding and addictive effects of opioids involves mu-opioid receptor (MOR) binding within the nucleus accumbens (NAcc), a region of the ventral striatum. GABAergic neurotransmission in the NAcc potentiates the rewarding response to opioids, and in fact, drugs that stimulate GABAergic activity are also addictive, a phenomenon mediated in part by endogenous opioids. However, the neuroanatomical relationship between opioid and GABA systems is still unclear, and further study of the interaction between these neurotransmitter systems in the reward pathway is warranted. We report evidence supporting the direct interaction between GABAergic and opioidergic neurotransmitter systems within the mouse NAcc. Male and female FVB/NJ mice (12-16 months of age) were euthanized via carbon dioxide inhalation and brains processed for histology and immunohistochemistry (IHC). Coronal cryosections (10-12 um in thickness) were taken through the NAcc at the level of the anterior commissure. A mouse monoclonal antibody against GAD67, an enzyme catalyzing GABA production, was used in conjunction with an anti-mouse rhodamine red-X-labeled secondary antibody to identify GABAergic neurons in the NAcc. Alternating sections were stained for MOR using a fluorescein isothiocyanate (FITC)-conjugated rabbit polyclonal anti-MOR1 antibody. DAPI (4′,6-diamidino-2-phenylindole) was used to counterstain the nuclei. As expected, fluorescence microscopy results show that GAD67 staining is localized predominately in the neuronal cytoplasm, with approximately 40% of the population staining. The MOR1-FITC stain showed localization within the cytoplasm and plasma membrane as expected, however, there was also significant staining in the nuclear membrane and neuronal nucleus. MOR1-FITC was present in approximately 35% of the neuronal population. In separate experiments, we used double-immunostaining to study the co-expression of MOR1 and GAD67 within the same NAcc neurons. A similar localization pattern was detected with a small subset, approximately 2%, of neurons expressing both labels. There are few published reports of GAD67 and MOR1 co-expression within neurons of the NAcc. Previous studies of MOR expression show the receptor to be localized to the plasma membrane and, to a smaller degree, intracellularly. Here we found the MOR1 staining to be predominantly in the nucleus and nuclear membrane, with minimal expression on the plasma membrane. Further studies are in progress to validate the nuclear expression of MOR in GABAergic NAcc neurons. Results of the study suggest that a subset of mouse NAcc neurons express both MOR1 and GAD67, providing a direct intracellular link between opioid and GABAergic systems in the reward pathway. Preliminary intranuclear localization of MOR suggests a novel signaling pathway that may be important in fully elucidating neurobiological mechanisms underlying behaviors related to reward and addiction.

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Section: Colocalization Of Gad67 and Mor1 In Mouse Naccmentioning

confidence: 99%

Colocalization of MOR1 and GAD67 in Mouse Nucleus Accumbens

Hinkle

Dedkov

Buono

et al. 2019

Preprint

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“…Proteomic analysis with 2-DE can simultaneously detect changes of multiple proteins in plasma often detected differentially expressed proteins are common abundant plasma proteins and their diagnostic value may be limited. Twodimensional electrophoresis (2-DE) has been used for the discovery of circulating auto-antibodies in cancer patients and annexins I and II were reported as specific antigens in sera from patients with lung [Nolen and Lokshin, 2013]; b-2 microglobulin [Yang et al, 2009] apolipoprotein [Podzielinski et al, 2013]; gene-expression in HE4 [Ferraro et al, 2013 [Du et al, 2013]; AGR2 [Li et al, 2015c]; ubiquitin ligase [Goka and Lippman, 2015]; ferritin light chain [Jezequel et al, 2012] Gastric cancer a1-antitrypsin precursor [Hsu et al, 2007]; pepsinogen C [Terasawa et al, 2014]; Cathepsin B [Ebert et al, 2005]; galectin-1/-3 [Thijssen et al, 2015]; miR-214 [Zhang et al, 2015b]; angiopoietinlike protein 2 [Yoshinaga et al, 2015]; MOR1 [Yao et al, 2015]; circular RNA [Li et al, 2015a] Liver cancer Galectin-1/-3 [Thijssen et al, 2015]; CHI3L1/MASP2 [Ding et al, 2014]; Sall4, Glypican-3, dickkopf-1 and talin-1 [Chatterjee and Mitra, 2015] …”

Section: Plasma Proteomics In Tumorsmentioning

confidence: 99%

“…Fibrinogen A fragment [van den Broek et al, 2010]; BAG6, DDX39, ANXA8, COX4 [Calderon-Gonzalez et al, 2015]; GCDFP-15 [Darb-Esfahani et al, 2014]; Versican [Du et al, 2013]; AGR2 [Li et al, 2015c]; ubiquitin ligase [Goka and Lippman, 2015]; ferritin light chain [Jezequel et al, 2012] Gastric cancer a1-antitrypsin precursor [Hsu et al, 2007]; pepsinogen C [Terasawa et al, 2014]; Cathepsin B [Ebert et al, 2005]; galectin-1/-3 [Thijssen et al, 2015]; miR-214 [Zhang et al, 2015b]; angiopoietinlike protein 2 [Yoshinaga et al, 2015]; MOR1 [Yao et al, 2015]; circular RNA [Li et al, 2015a]…”

Section: Breast Cancermentioning

confidence: 99%

Translational Research and Plasma Proteomic in Cancer

Santini

Giovane

Auletta

et al. 2015

J of Cellular Biochemistry

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Proteomics is a recent field of research in molecular biology that can help in the fight against cancer through the search for biomarkers that can detect this disease in the early stages of its development. Proteomic is a speedily growing technology, also thanks to the development of even more sensitive and fast mass spectrometry analysis. Although this technique is the most widespread for the discovery of new cancer biomarkers, it still suffers of a poor sensitivity and insufficient reproducibility, essentially due to the tumor heterogeneity. Common technical shortcomings include limitations in the sensitivity of detecting low abundant biomarkers and possible systematic biases in the observed data. Current research attempts are trying to develop high-resolution proteomic instrumentation for high-throughput monitoring of protein changes that occur in cancer. In this review, we describe the basic features of the proteomic tools which have proven to be useful in cancer research, showing their advantages and disadvantages. The application of these proteomic tools could provide early biomarkers detection in various cancer types and could improve the understanding the mechanisms of tumor growth and dissemination.

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“…Concurrent translational investigation has revealed that increased expression of µ-opioid receptors (MOR) in non-small cell lung cancer [3], prostate cancer [4], gastric cancer [5] and melanoma [6, 7] is associated with greater degree of metastasis [8]. Further laboratory work reveals multiple interactions between opioids and transcription factors for tumor growth, immunomodulation and vascular endothelial growth factor (VEGF) expression, leading to modulation of neovascularization [9].…”

Section: Introductionmentioning

confidence: 99%

The effect of anesthetic technique on µ-opioid receptor expression and immune cell infiltration in breast cancer

et al. 2018

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BackgroundClinical histological studies demonstrate that the distribution of natural killer (NK) cells, other immune cells and μ-opioid receptors (MOR) within cancer tissue can predict cancer prognosis. No clinical study has evaluated whether anesthetic technique influences immune cell and MOR expression within human breast cancer.MethodsExcised preoperative biopsies and intraoperative breast cancer specimens from 20 patients randomly chosen from patients previously enrolled in an ongoing, prospective, randomized trial (NCT00418457) investigating the effect of anesthetic technique on long-term breast cancer outcome were immunohistochemically stained and microscopically examined by two independent investigators, masked to randomization, to quantify MOR and immune cell infiltration: CD56, CD57 (NK cells), CD4 (T helper cells), CD8 (cytotoxic T cells) and CD68 (macrophages). Patients had been randomized to receive either a propofol–paravertebral anesthetic with continuing analgesia (PPA, n = 10) or balanced general anesthetic with opioid analgesia (GA, n = 10).ResultsThere were no differences between the groups in staining intensity in preoperative biopsy specimens. Expression intensity values (median 25–75%) for MOR in intraoperative resected biopsy were higher in GA 8.5 (3–17) versus PPA 1 (0–10), p = 0.04. The numbers of MOR-positive cells were also higher in GA patients. Expression and absolute numbers of CD56, CD57, CD4 and CD68 were similar in resected tumor in both groups.ConclusionGeneral anesthesia with opioid analgesia increased resected tumor MOR expression compared with propofol–paravertebral anesthetic technique, but the anesthetic technique did not significantly influence the expression of immune cell markers.

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MOR1 Expression in Gastric Cancer: A Biomarker Associated With Poor Outcome

Cited by 33 publications

References 34 publications

Colocalization of MOR1 and GAD67 in Mouse Nucleus Accumbens

Colocalization of MOR1 and GAD67 in Mouse Nucleus Accumbens

Translational Research and Plasma Proteomic in Cancer

The effect of anesthetic technique on µ-opioid receptor expression and immune cell infiltration in breast cancer

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