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Analyzing Tumor Gene Expression Factors with the CorExplorer Web Portal
Published on: October 11, 2019
New Target Genes for Tumor-derived Soluble Factors in Primary Monocytes
Tanja Hofmann1, Bärbel Schmitt1, Brigitte Mack1
1Department of Otorhinolaryngology, Ludwig-Maximilians-University, D-81377 Munich, Germany.
Background:
Tumor cells have developed several strategies to escape the immune system. One of these strategies consists of the secretion of immunosuppressive factors like interleukin-10 or prostaglandin E2 (PGE2), which impair the immune system. We have demonstrated recently that tumor-derived PGE2 down-regulates the expression of the integrin Mac-1 and the chemokine receptor CCR5 on primary monocytes, resulting in reduced adhesion and migration.
Materials And Methods:
In order to identify new target genes for tumor-derived factors in monocytes, we set up an in vitro system consisting of cDNA micro arrays and 2D gel electrophoresis.
Results:
We identified 25 genes that were differentially expressed upon incubation of cells in conditioned tumor cell supernatants as compared to cells incubated in cell culture medium. We describe in more detail that IL-1β secretion is induced by tumor supernatants and that IL-1β overexpression is also evident in monocytes from tumor patients in vivo, where expression correlates with the tumor stage. In addition, up-regulation of the plasminogen activator inhibitor-2, PAI-2, and down-regulation of the urokinase-type plasminogen activator receptor, uPAR, resulted in a reduced capability of monocytes to degrade and invade extracellular matrices.
Conclusion:
In summary, we describe interesting novel targets of soluble tumor-derived factors that are probably involved in the tumor-mediated immunosuppression commonly found in cancer patients.
Insights
Tumor cells secrete factors that suppress the immune system. This study identifies novel gene targets in monocytes, including IL-1β, involved in tumor-induced immunosuppression and disease progression.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Tumor cells evade immune detection through immunosuppressive factors like prostaglandin E2 (PGE2).
- Tumor-derived PGE2 reduces monocyte adhesion and migration by down-regulating Mac-1 and CCR5.
- Understanding these tumor-mediated immune evasion mechanisms is crucial for cancer therapy.
Purpose of the Study:
- To identify novel genes in monocytes targeted by soluble tumor-derived factors.
- To elucidate molecular mechanisms of tumor-induced immunosuppression.
Main Methods:
- Utilized an in vitro system with cDNA microarrays and 2D gel electrophoresis.
- Analyzed gene expression changes in monocytes exposed to conditioned tumor cell supernatants.
Main Results:
- Identified 25 differentially expressed genes in monocytes upon exposure to tumor supernatants.
- Discovered tumor supernatants induce interleukin-1 beta (IL-1β) secretion, which is upregulated in monocytes from cancer patients and correlates with tumor stage.
- Observed altered expression of plasminogen activator inhibitor-2 (PAI-2) and urokinase-type plasminogen activator receptor (uPAR), impacting monocyte extracellular matrix degradation.
Conclusions:
- Identified novel molecular targets of soluble tumor-derived factors involved in immunosuppression.
- IL-1β, PAI-2, and uPAR are key mediators of tumor-induced immune evasion.
- Findings provide insights into mechanisms of cancer immune evasion and potential therapeutic targets.
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