Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli
Background: Opioid receptors are naloxone-sensitive (MOP [mu: μ], DOP [delta: δ], and KOP [kappa: κ]) and naloxone-insensitive Nociceptin/Orphanin FQ (N/OFQ) peptide receptor (NOP). Clinically, most opioid analgesics target MOP. Angiogenesis is the formation of new blood vessels and involves endothe...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | BJA Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772609622001095 |
| _version_ | 1811196110236024832 |
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| author | Despina Giakomidi Sonja Khemiri Wadhah Mahbuba David G. McVey Fatin Al-Janabi Remo Guerrini Girolamo Calo Shu Ye David G. Lambert |
| author_facet | Despina Giakomidi Sonja Khemiri Wadhah Mahbuba David G. McVey Fatin Al-Janabi Remo Guerrini Girolamo Calo Shu Ye David G. Lambert |
| author_sort | Despina Giakomidi |
| collection | DOAJ |
| description | Background: Opioid receptors are naloxone-sensitive (MOP [mu: μ], DOP [delta: δ], and KOP [kappa: κ]) and naloxone-insensitive Nociceptin/Orphanin FQ (N/OFQ) peptide receptor (NOP). Clinically, most opioid analgesics target MOP. Angiogenesis is the formation of new blood vessels and involves endothelial cell activation, proliferation, and migration. The effect of opioids on this process is controversial with no data for NOP receptor ligands. Methods: We used patient-derived human umbilical vein endothelial cells (HUVECs) treated with media from the Michigan Cancer Foundation-7 (MCF-7) breast cancer cells or vascular endothelial growth factor (VEGF; 10 ng ml−1) and fibroblast growth factor (FGF; 10 ng ml−1) as angiogenic stimuli. We have measured (i) NOP/MOP messenger RNA, (ii) receptor protein using N/OFQATTO594 and DermorphinATTO488 as fluorescent probes for NOP and MOP, and (iii) NOP/MOP function in a wound healing assay (crude measure of migration that occurs during angiogenesis). Results: HUVEC lines from 32 patients were used. Using all 32 lines, mRNA for NOP but not MOP was detected. This was unaffected by media from MCF-7 cells or VEGF/FGF. There was no binding of either N/OFQATTO594(NOP) or DermorphinATTO488(MOP) in the absence or presence of angiogenic stimuli (six lines tested). In the absence of MOP mRNA, this was expected. Whilst MCF-7 conditioned medium (not VEGF/FGF) reduced wound healing per se (14 lines tested), there was no effect of N/OFQ (NOP ligand) or morphine (MOP ligand). Conclusions: Media from MCF-7 breast cancer cells or VEGF/FGF as angiogenic stimuli did not influence NOP translation into receptor protein. MOP was absent. In the absence of constitutive or inducible MOP/NOP, there was no effect on wound healing as a measure of angiogenesis. |
| first_indexed | 2024-04-12T00:53:15Z |
| format | Article |
| id | doaj.art-1dee7627c7d04f38879e5822c85bdbf7 |
| institution | Directory Open Access Journal |
| issn | 2772-6096 |
| language | English |
| last_indexed | 2024-04-12T00:53:15Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | BJA Open |
| spelling | doaj.art-1dee7627c7d04f38879e5822c85bdbf72022-12-22T03:54:40ZengElsevierBJA Open2772-60962022-12-014100110Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuliDespina Giakomidi0Sonja Khemiri1Wadhah Mahbuba2David G. McVey3Fatin Al-Janabi4Remo Guerrini5Girolamo Calo6Shu Ye7David G. Lambert8Department of Cardiovascular Sciences, Anaesthesia, Critical Care and Pain Management, Hodgkin Building, University of Leicester, Leicester, UKDepartment of Cardiovascular Sciences, Anaesthesia, Critical Care and Pain Management, Hodgkin Building, University of Leicester, Leicester, UKDepartment of Cardiovascular Sciences, Anaesthesia, Critical Care and Pain Management, Hodgkin Building, University of Leicester, Leicester, UKDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UKDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UKDepartment of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara, ItalyDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, ItalyDepartment of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UKDepartment of Cardiovascular Sciences, Anaesthesia, Critical Care and Pain Management, Hodgkin Building, University of Leicester, Leicester, UK; Corresponding author.Background: Opioid receptors are naloxone-sensitive (MOP [mu: μ], DOP [delta: δ], and KOP [kappa: κ]) and naloxone-insensitive Nociceptin/Orphanin FQ (N/OFQ) peptide receptor (NOP). Clinically, most opioid analgesics target MOP. Angiogenesis is the formation of new blood vessels and involves endothelial cell activation, proliferation, and migration. The effect of opioids on this process is controversial with no data for NOP receptor ligands. Methods: We used patient-derived human umbilical vein endothelial cells (HUVECs) treated with media from the Michigan Cancer Foundation-7 (MCF-7) breast cancer cells or vascular endothelial growth factor (VEGF; 10 ng ml−1) and fibroblast growth factor (FGF; 10 ng ml−1) as angiogenic stimuli. We have measured (i) NOP/MOP messenger RNA, (ii) receptor protein using N/OFQATTO594 and DermorphinATTO488 as fluorescent probes for NOP and MOP, and (iii) NOP/MOP function in a wound healing assay (crude measure of migration that occurs during angiogenesis). Results: HUVEC lines from 32 patients were used. Using all 32 lines, mRNA for NOP but not MOP was detected. This was unaffected by media from MCF-7 cells or VEGF/FGF. There was no binding of either N/OFQATTO594(NOP) or DermorphinATTO488(MOP) in the absence or presence of angiogenic stimuli (six lines tested). In the absence of MOP mRNA, this was expected. Whilst MCF-7 conditioned medium (not VEGF/FGF) reduced wound healing per se (14 lines tested), there was no effect of N/OFQ (NOP ligand) or morphine (MOP ligand). Conclusions: Media from MCF-7 breast cancer cells or VEGF/FGF as angiogenic stimuli did not influence NOP translation into receptor protein. MOP was absent. In the absence of constitutive or inducible MOP/NOP, there was no effect on wound healing as a measure of angiogenesis.http://www.sciencedirect.com/science/article/pii/S2772609622001095angiogenesiscancerconfocal microscopyHUVE cellsnociceptin/orphanin FQ receptors (NOP) |
| spellingShingle | Despina Giakomidi Sonja Khemiri Wadhah Mahbuba David G. McVey Fatin Al-Janabi Remo Guerrini Girolamo Calo Shu Ye David G. Lambert Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli BJA Open angiogenesis cancer confocal microscopy HUVE cells nociceptin/orphanin FQ receptors (NOP) |
| title | Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli |
| title_full | Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli |
| title_fullStr | Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli |
| title_full_unstemmed | Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli |
| title_short | Nociceptin/Orphanin FQ receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli |
| title_sort | nociceptin orphanin fq receptor expression in primary human umbilical vein endothelial cells is not regulated by exposure to breast cancer cell media or angiogenic stimuli |
| topic | angiogenesis cancer confocal microscopy HUVE cells nociceptin/orphanin FQ receptors (NOP) |
| url | http://www.sciencedirect.com/science/article/pii/S2772609622001095 |
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