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Updated: Aug 22, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Endogenous morphinergic signaling and tumor growth
Patrick Cadet1, Mads Rasmussen, Wei Zhu
1Neuroscience Research Institute, State University of New York, College at Old Westbury, Old Westbury, NY 11568-0210, USA.
Abstract:
The mu3 opiate receptor subtype has been characterized by various binding assays as opiate alkaloid selective (e.g. morphine) and opioid peptide (e.g. methionine enkephalin) insensitive. This opiate receptor subtype has been found on human, including cancer cell lines, and invertebrate tissues, demonstrating that it has been conserved during evolution. Furthermore, in numerous reports, this receptor is coupled to constitutive nitric oxide release. In this regard, for example, morphine immune down regulating activities parallels those actions formerly attributed to nitric oxide. We have now identified the mu3 receptor at the molecular level and sequence analysis of the isolated cDNA suggests that it is a novel, alternatively spliced variant of the mu opiate receptor gene (MOR). Furthermore, using Northern blot, reverse transcription coupled to polymerase chain reaction (RT-PCR) and sequence analysis, we have demonstrated the expression of this new mu variant in human vascular tissue, mononuclear cells, polymorphonuclear cells, and human neuroblastoma cells. The presence of this mu splice variant, adds to the growing body of evidence supporting the hypothesis that morphine is an endogenous signaling molecule in neural, immune and vascular systems. In addition to their use in the treatment of pain, opioid peptides appear to be important in the growth regulation of normal and neoplastic tissue. This review will focus on the influence of opiate alkaloids, e.g., morphine, on tumor growth, with emphasis on immuno-regulatory and antiproliferative mechanisms.
Insights
Researchers identified the mu3 opiate receptor, a novel variant of the mu opiate receptor gene. This discovery supports morphine as an endogenous signaling molecule in neural, immune, and vascular systems.
Area of Science:
- Pharmacology
- Molecular Biology
- Neuroscience
Background:
- The mu3 opiate receptor subtype is selective for opiate alkaloids like morphine and insensitive to opioid peptides.
- This receptor is conserved across species and found in human and invertebrate tissues, often linked to nitric oxide release.
- Morphine's immune-modulating effects may be mediated by nitric oxide pathways associated with the mu3 receptor.
Purpose of the Study:
- To identify the mu3 opiate receptor at the molecular level.
- To characterize its gene variant and expression patterns.
- To explore the role of morphine as an endogenous signaling molecule.
Main Methods:
- Molecular identification and sequence analysis of the mu3 receptor cDNA.
- Northern blot analysis to detect gene expression.
- Reverse transcription coupled to polymerase chain reaction (RT-PCR) for expression analysis.
- Sequence analysis of the identified variant.
Main Results:
- The mu3 opiate receptor was identified as a novel, alternatively spliced variant of the mu opiate receptor gene (MOR).
- Expression of this mu splice variant was confirmed in human vascular tissue, mononuclear cells, polymorphonuclear cells, and neuroblastoma cells.
- Findings support morphine's role as an endogenous signaling molecule in multiple physiological systems.
Conclusions:
- The identification of the mu3 receptor splice variant provides molecular evidence for morphine's endogenous signaling functions.
- This discovery has implications for understanding morphine's role in neural, immune, and vascular systems.
- Further research into opiate alkaloids' effects on tumor growth, including immuno-regulatory and antiproliferative mechanisms, is warranted.
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