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New Molecular and Mechanistic Basis for the Inflammasome Manipulation in Cancer and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 3383

Special Issue Editors


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Guest Editor
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Tatarstan, Russia
Interests: immune response; cytotoxic T cells; B cells; antibodies; autoantibodies; cytokines; antibody dependent cytotoxicity; pathogen associated molecular patterns; pathogen recognition receptors
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Co-Guest Editor
Department of Fundamental Sciences, Faculty of Dentistry, Bursa Uludag University, 16059 Bursa, Turkey
Interests: immune response; cytotoxic T cells; cytokines; inflammasome; molecular regulation of inflammasome; cancer pathogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammation is shown to be a risk factor of tumor development. Inflammation is characterized by the release of numerous pro-inflammatory cytokines, growth factors, increased blood vessel permeability and the migration of leukocytes. Among cytokines, IL-1β and IL-18, products of inflammasome, are the leading mediators of inflammation. Inflammasomes are the multiprotein complexes formed when pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patters (DAMPs) are present. Inflammasomes could be activated by multiple endogenous and exogenous stimuli, such as potassium ions efflux, reactive oxygen species, viruses, bacterial toxins, etc. The active inflammasome cleaves the pro-caspase 1 to release caspase 1, a proteolytic enzyme. Caspase 1 subsequently cleaves pro-IL-1β and pro-IL-18; therefore, the active forms of these cytokines are produced.

By releasing pro-inflammatory cytokines, inflammasomes could contribute to the initiation and maintenance of local inflammation. This inflammatory milieu could support cell proliferation, alter transcriptional activity and promote angiogenesis. Therefore, the regulation of inflammasome activity could be a novel approach for cancer treatment. We invite authors to submit the original research papers, case reports, and review articles with the following potential list of topics:

  1. The molecular regulation of inflammasome activation;
  2. The role of inflammasomes in cancer pathogenesis;
  3. Molecular mechanisms of novel therapeutic approaches for cancer treatment targeting inflammasomes;
  4. The mechanistic manipulation of inflammasome activity that aims to treat cancer and other diseases;
  5. Role of PAMPS, DAMPS and PRRs in immune responses to cancer.

Dr. Svetlana F. Khaiboullina
Dr. Gülçin Tezcan
Guest Editors

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Keywords

  • inflammation
  • molecular recognition
  • inflammasome role in cancer 
  • inflammasome role in diseases 
  • cancer treatment targeting inflammasome
  • inflammasome activity manipulation

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Published Papers (1 paper)

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Research

24 pages, 16390 KiB  
Article
Blocking the Hormone Receptors Modulates NLRP3 in LPS-Primed Breast Cancer Cells
by Shaimaa Hamza, Ekaterina E. Garanina, Mohammad Alsaadi, Svetlana F. Khaiboullina and Gulcin Tezcan
Int. J. Mol. Sci. 2023, 24(5), 4846; https://doi.org/10.3390/ijms24054846 - 2 Mar 2023
Cited by 1 | Viewed by 2953
Abstract
NOD-like receptor protein 3 (NLRP3) may contribute to the growth and propagation of breast cancer (BC). The effect of estrogen receptor-α (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) on NLRP3 activation in BC remains unknown. Additionally, our knowledge [...] Read more.
NOD-like receptor protein 3 (NLRP3) may contribute to the growth and propagation of breast cancer (BC). The effect of estrogen receptor-α (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) on NLRP3 activation in BC remains unknown. Additionally, our knowledge of the effect of blocking these receptors on NLRP3 expression is limited. We used GEPIA, UALCAN, and the Human Protein Atlas for transcriptomic profiling of NLRP3 in BC. Lipopolysaccharide (LPS) and adenosine 5′-triphosphate (ATP) were used to activate NLRP3 in luminal A MCF-7 and in TNBC MDA-MB-231 and HCC1806 cells. Tamoxifen (Tx), mifepristone (mife), and trastuzumab (Tmab) were used to block ER-α, PR, and HER2, respectively, on inflammasome activation in LPS-primed MCF7 cells. The transcript level of NLRP3 was correlated with ER-ɑ encoding gene ESR1 in luminal A (ER-α+, PR+) and TNBC tumors. NLRP3 protein expression was higher in untreated and LPS/ATP-treated MDA-MB-231 cells than in MCF7 cells. LPS/ATP-mediated NLRP3 activation reduced cell proliferation and recovery of wound healing in both BC cell lines. LPS/ATP treatment prevented spheroid formation in MDA-MB-231 cells but did not affect MCF7. HGF, IL-3, IL-8, M-CSF, MCP-1, and SCGF-b cytokines were secreted in both MDA-MB-231 and MCF7 cells in response to LPS/ATP treatment. Tx (ER-α inhibition) promoted NLRP3 activation and increased migration and sphere formation after LPS treatment of MCF7 cells. Tx-mediated activation of NLRP3 was associated with increased secretion of IL-8 and SCGF-b compared to LPS-only-treated MCF7 cells. In contrast, Tmab (Her2 inhibition) had a limited effect on NLRP3 activation in LPS-treated MCF7 cells. Mife (PR inhibition) opposed NLRP3 activation in LPS-primed MCF7 cells. We have found that Tx increased the expression of NLRP3 in LPS-primed MCF7. These data suggest a link between blocking ER-α and activation of NLRP3, which was associated with increased aggressiveness of the ER-α+ BC cells. Full article
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