Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC- -dependent mechanism

Paone, Alessio; Starace, Donatella; Galli, Roberta; Padula, Fabrizio; Cesaris, Paola De; Filippini, Antonio; Ziparo, Elio; Riccioli, Anna

doi:10.1093/carcin/bgn149

Cited by 151 publications

(153 citation statements)

References 46 publications

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“…We further studied the mechanism how PGN induces THP-1 apoptosis. We showed that in THP-1 supernatant adding in with specific mAB of TNF-α, the apoptosis effect of THP-1 was decreased after PGN stimulation, these data demonstrate that PGN induces the apoptosis of human leukemia THP-1 cells in a TNF-α-dependent way, and, there are reports demonstrated that activation of TLRs induced tumor cells apoptosis by other stimulating mechanism (Paone et al, 2008). However, some reports demonstrated that activation of TLRs can trigger proliferation and survival of multiple cancer cells.…”

Section: Discussionsupporting

confidence: 54%

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Peptidoglycans Promotes Human Leukemic THP-1 Cell Apoptosis and Differentiation

Wang¹,

Xiao²,

Duan³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Tolllike receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-1β, interleukin-8 and TNF-α and apoptosis of THP-1 with PGN dose and time dependence. Moreover , in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-α-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers.

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Section: Discussionsupporting

confidence: 54%

“…The reports have previously demonstrated that ligand recognition by TLRs triggers human prostate cancer cells and glioma cells apoptosis through TLR3 and TLR9 respectively (Paone et al, 2008). Recently, we also demonstrated that PGN, the ligand of TLR2 induced THP-1 apoptosis by time-and dose-dependent manner.…”

Section: Discussionmentioning

confidence: 60%

Peptidoglycans Promotes Human Leukemic THP-1 Cell Apoptosis and Differentiation

Wang¹,

Xiao²,

Duan³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…cM362-140 activated TICAM-1 for DC maturation, but barely induced chemokine production or necroptosis in tumour cells ( Supplementary Fig. 10), which were reported as a direct action of poly(I:C) 29,30 . Therefore, cM362-140 eliminates major inflammatory responses caused by poly(I:C).…”

Section: Discussionmentioning

confidence: 92%

Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo

et al. 2015

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Ligand stimulation of the Toll-like receptors (TLRs) triggers innate immune response, cytokine production and cellular immune activation in dendritic cells. However, most TLR ligands are microbial constituents, which cause inflammation and toxicity. Toxic response could be reduced for secure immunotherapy through the use of chemically synthesized ligands with defined functions. Here we create an RNA ligand for TLR3 with no ability to activate the RIG-I/MDA5 pathway. This TLR3 ligand is a chimeric molecule consisting of phosphorothioate ODN-guided dsRNA (sODN-dsRNA), which elicits far less cytokine production than poly(I:C) in vitro and in vivo. The activation of TLR3/TICAM-1 pathway by sODN-dsRNA effectively induces natural killer and cytotoxic T cells in tumour-loaded mice, thereby establishing antitumour immunity. Systemic cytokinemia does not occur following subcutaneous or even intraperitoneal administration of sODN-dsRNA, indicating that TICAM-1 signalling with minute local cytokines sufficiently activate dendritic cells to prime tumoricidal effectors in vivo.

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“…This reaction may be due to the established balance favoring apoptosis rather than the proliferation of cancer cells under TLR ligation [68]. This balance may depend on the concentration of certain cytokines and the time of stimulation [69].…”

Section: The Results Of Tlr Activation -Tlrs In Carcinogenesismentioning

confidence: 99%

Toll-like receptors and their role in carcinogenesis and anti-tumor treatment

Wolska

Lech‐Marańda

Robak

2009

Cellular and Molecular Biology Letters

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Toll-like receptors (TLRs) have been described as major components of the innate immune system, recognizing the conserved molecular structures found in the large groups of pathogens called pathogen-associated molecular patterns (PAMPs). TLR expression is ubiquitous, from epithelial to immunocompetent cells. TLR ligation triggers several adapter proteins and downstream kinases, leading to the induction of key pro-inflammatory mediators but also anti-inflammatory and anti-tumor cytokines. The result of this activation goes beyond innate immunity to shape the adaptive responses against pathogens and tumor cells, and maintains host homeostasis via cell debris utilization. TLRs have already become potent targets in infectious disease treatment and vaccine therapy and in neoplastic disease treatment, due to their ability to enhance antigen presentation. However, some studies show the dual effect of TLR stimulation on malignant cells: they can be proapoptotic or promote survival under different conditions. It is therefore crucial to design further studies assessing the biology of these receptors in normal and transformed cells. The established role of TLRs in human disease therapy is based on TLR7 and TLR4 agonists, respectively for the novel treatment of some types of skin cancer and for the anti-hepatitis B virus vaccine. Some clinical trials involving TLR agonists as potent enhancers of the anti-tumor response in solid tumors have begun.

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Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC- -dependent mechanism

Cited by 151 publications

References 46 publications

Peptidoglycans Promotes Human Leukemic THP-1 Cell Apoptosis and Differentiation

Peptidoglycans Promotes Human Leukemic THP-1 Cell Apoptosis and Differentiation

Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo

Toll-like receptors and their role in carcinogenesis and anti-tumor treatment

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