Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis

Muresan, Ximena Maria; Slabáková, Eva; Procházková, Jiřina; Drápela, Stanislav; Fedr, Radek; Pícková, Markéta; Vacek, Ondřej; Víchová, Ráchel; Suchánková, Tereza; Bouchal, Jan; Kurfürstová, Daniela; Král, Milan; Hulínová, Tereza; Sýkora, Radek; Študent, Vladimír; Hejret, Václav; Weerden, Wytske M. van; Puhr, Martin; Pustka, Václav; Potěšil, David; Zdráhal, Zbyněk; Čulig, Zoran; Souček, Karel

doi:10.1016/j.ajpath.2022.05.009

Cited by 5 publications

(3 citation statements)

References 55 publications

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“…All this evidence indicates that TLR3 activation in a tumor and its microenvironment by endogenous ligands can induce tumor survival and progression. A recent study showed that TLR3 overexpression in prostate cancer cells induces cancer invasion while its activation triggers apoptosis, confirming once again the double-edged sword nature of TLR3 [ 116 ]. Tavora et al recently revealed that endothelial cells have a direct instructive role in driving metastatic dissemination: tumor-derived dsRNAs induce TLR3 and SLIT2, leading to intravasation [ 117 ].…”

Section: Direct Impact Of Necrotic Products On Malignant Cells—role O...mentioning

confidence: 65%

Dialog beyond the Grave: Necrosis in the Tumor Microenvironment and Its Contribution to Tumor Growth

Zapletal

Vasiljevic

Busson

et al. 2023

IJMS

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Damage-associated molecular patterns (DAMPs) are endogenous molecules released from the necrotic cells dying after exposure to various stressors. After binding to their receptors, they can stimulate various signaling pathways in target cells. DAMPs are especially abundant in the microenvironment of malignant tumors and are suspected to influence the behavior of malignant and stromal cells in multiple ways often resulting in promotion of cell proliferation, migration, invasion, and metastasis, as well as increased immune evasion. This review will start with a reminder of the main features of cell necrosis, which will be compared to other forms of cell death. Then we will summarize the various methods used to assess tumor necrosis in clinical practice including medical imaging, histopathological examination, and/or biological assays. We will also consider the importance of necrosis as a prognostic factor. Then the focus will be on the DAMPs and their role in the tumor microenvironment (TME). We will address not only their interactions with the malignant cells, frequently leading to cancer progression, but also with the immune cells and their contribution to immunosuppression. Finally, we will emphasize the role of DAMPs released by necrotic cells in the activation of Toll-like receptors (TLRs) and the possible contributions of TLRs to tumor development. This last point is very important for the future of cancer therapeutics since there are attempts to use TLR artificial ligands for cancer therapeutics.

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Section: Direct Impact Of Necrotic Products On Malignant Cells—role O...mentioning

confidence: 65%

Dialog beyond the Grave: Necrosis in the Tumor Microenvironment and Its Contribution to Tumor Growth

Zapletal

Vasiljevic

Busson

et al. 2023

IJMS

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“…But despite that effect, a contrary role of TLR3 in tumor progression and invasion has also been proposed. Transcriptomic analysis of TLR3-overexpressing PCa cell lines revealed enriched genes that are involved in regulation of cell migration and tumor invasion (39). In parallel, Schulz and González-Reyes proved that high expression of TLR3 may lead to PCa biochemical recurrence (40,41).…”

Section: Discussionmentioning

confidence: 98%

Gut microbiota-derived short-chain fatty acids promote prostate cancer progression through inducing cancer cell autophagy and M2 macrophage polarization

Liu

Zhou

et al. 2022

Preprint

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Objective: Emerging research have reported the regulative role of gut microbiota-derived short-chain fatty acids (SCFAs) within tumor microenvironment. In previous study we have demonstrated abnormal gut microbial composition in castration-resistant prostate cancer (CRPC) patients, here we sought to reveal the mechanism of SCFAs as a mediator linking microbiota dysbiosis and prostate cancer (PCa) progression. Methods:By using transgenic TRAMP mouse model, PCa patient samples, in vitro PCa cell transwell assay, and macrophage recruitment assay, we examined the effects of fecal microbiota transplantation (FMT) and SCFAs on PCa progression. Results: FMT using CRPC patients’ fecal suspension increased the abundance of SCFAs-producing gut microbiotas in TRAMP mice including Ruminococcus, Alistipes, Phascolarctobaterium, and correspondingly raised mice’s gut acetate and butyrate levels. CRPC FMT or SCFAs supplementation accelerated TRAMP mice’s cancer progression. In vitro, SCFAs enhanced PCa cells migration and invasion by inducing TLR3-triggered autophagy that further activated NF-κB and MAPK signalings. Also, PCa cell-derived CCL20 activated by SCFAs reprogrammed the tumor microenvironment by recruiting more macrophage infiltration and simultaneously inducing M2 macrophage polarization, which in turn further strengthened PCa cells invasiveness. Finally in a large cohort of 362 PCa patients from our department, we demonstrated that CCL20 expression in prostate was positively correlated with Gleason grade, pre-operative PSA, neural invasion, seminal vesical invasion, and was negatively correlated with post-operative biochemical recurrence-free survival. Gut microbiota dysbiosis-related CCL20 could be a biomarker for predicting prognosis in PCa patients. Conclusion: Collectively, gut microbiota dysbiosis-derived SCFAs promoted PCa progression through inducing cancer cell autophagy and M2 macrophage polarization. Intervention of SCFAs-producing microbiotas may be a useful strategy in the manipulation of CRPC.

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“…But despite that effect, a contrary role of TLR3 in tumor progression and invasion has also been proposed. Transcriptomic analysis of TLR3-overexpressing PCa cell lines revealed enriched genes that are involved in regulation of cell migration and tumor invasion [39] . In parallel, Schulz and González-Reyes proved that high expression of TLR3 may lead to PCa biochemical recurrence [40 , 41] .…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota-derived short-chain fatty acids promote prostate cancer progression via inducing cancer cell autophagy and M2 macrophage polarization

Liu

Zhou

et al. 2023

Neoplasia

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Toll-Like Receptor 3 Overexpression Induces Invasion of Prostate Cancer Cells, whereas Its Activation Triggers Apoptosis

Cited by 5 publications

References 55 publications

Dialog beyond the Grave: Necrosis in the Tumor Microenvironment and Its Contribution to Tumor Growth

Dialog beyond the Grave: Necrosis in the Tumor Microenvironment and Its Contribution to Tumor Growth

Gut microbiota-derived short-chain fatty acids promote prostate cancer progression through inducing cancer cell autophagy and M2 macrophage polarization

Gut microbiota-derived short-chain fatty acids promote prostate cancer progression via inducing cancer cell autophagy and M2 macrophage polarization

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