Bidirectional Regulation of COX-2 Expression Between Cancer Cells and Macrophages
Maria Isabel Carvalho1,2,3, Rodolfo Bianchini3, Judit Fazekas-Singer3,4
1Animal and Veterinary Research Centre, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
Anticancer Research
|May 2, 2018
Summary
Tumor cells and immune cells (macrophages) influence cyclo-oxygenase-2 (COX2) levels in canine mammary tumors (CMT). This bidirectional regulation may create a tumor microenvironment that suppresses immune responses.
Area of Science:
- Oncology
- Immunology
- Veterinary Medicine
Background:
- Canine mammary tumors (CMT) exhibit complex interactions between tumor cells and the immune microenvironment.
- M2 macrophages are key immune cells implicated in tumor progression and immune suppression.
Purpose of the Study:
- To investigate the crosstalk between canine mammary tumor (CMT) cells and M2 macrophages.
- To determine the effect of this interaction on cyclo-oxygenase-2 (COX2) regulation within the tumor microenvironment.
Main Methods:
- Co-culture of Sh1b CMT cells with canine peripheral blood mononuclear cells (PBMCs) or differentiated THP1 monocytes (dTHP1).
- Co-culture of human cancer cell lines (BT474, HT29) with dTHP1.
- Flow cytometry was used to evaluate intracellular COX2 expression in cancer cells and immune cells.
Main Results:
- Co-culture with PBMCs induced COX2 overexpression in CMT cells.
- CMT cells attenuated COX2 expression in PBMCs (macrophages).
- dTHP1 prompted COX2 production in CMT and HT29 cells but reduced it in BT474 cells, while conditioned medium from cancer cells decreased dTHP1 COX2 expression.
Conclusions:
- Bidirectional regulation of COX2 occurs between cancer cells and monocytes/macrophages in CMT.
- This interaction may contribute to a tolerogenic tumor microenvironment, potentially hindering anti-tumor immunity.
Related Concept Videos
02:24Regulation of Expression Occurs at Multiple Steps
26.5K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
26.5K
02:24Regulation of Expression Occurs at Multiple Steps
4.0K
4.0K
01:23Regulation of Expression at Multiple Steps
1.4K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.4K
01:27Constitutive and Regulated Gene Expression
1.3K
Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
1.3K
01:58Cell Specific Gene Expression
16.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.6K
01:28pH Regulation in Cells
7.8K
pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
7.8K