Abstract
BackgroundMany types of tumors are organized in a hierarchy of heterogeneous cell populations with different molecular signature. Such heterogeneity may be associated with different responsiveness to microenvironment stimuli. In the present study, the effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA), as well-known mediators of inflammation, on cancerous behavior of three prostate tumor cells, LNCaP, PC3 and DU145, were investigated.MethodsExpression of TLR1-10, CD14 and MyD88 transcripts was investigated by RT-PCR. Protein expression of TLR2 and 4 was scrutinized by flow cytometry, immunofluorescent staining and Western blotting. Experiments were set up to assess the effects of LPS and LTA at different concentrations and times on cell proliferation, extracellular matrix invasion, adhesion and cytokine production.ResultsWe showed that prostate cancer cell lines differentially express TLR1-10, MyD88 and CD14 transcripts. DU145 failed to express TLR4 gene. Positively-identified TLR2 protein in all prostate cancer cells and TLR4 protein in PC3 and LNCaP by Western blotting was not accompanied by cell surface expression, as judged by flow cytometry. Immunofluorescent staining clearly demonstrated predominantly perinuclear localization of TLR2 and TLR4. LTA activation of all prostate cancer cells significantly increased cell proliferation. Regardless of lacking TLR4, DU145 cells proliferated in response to LPS treatment. While LPS caused increased invasiveness of LNCaP, invasive capacity of PC3 was significantly reduced after LPS or LTA stimulation. Stimulation of all prostate tumor cells with LTA was associated with increased cell adhesion and IL-8 production. IL-6 production, however, was differentially regulated by LPS stimulation in prostate tumor cells.ConclusionThe data shows that cancer cells originated from the same histologically origin exhibit heterogeneous response to the same TLR ligand. Therefore, a thorough and comprehensive judgment on how and to what extent a particular cancer is affected by TLR agonist could not be inferred by studying an individual cell line.
Highlights
Immune recognition of microorganisms is carried out by a set of receptors collectively referred to as pattern recognition receptors (PRR)
TLR1-10 and myeloid differentiation primary response gene 88 (MyD88) were differentially expressed by these cell lines with different densities
Of the TLR genes examined, LNCaP failed to express detectable levels of TLR7 and 8 and exhibited very low level expression of TLR2, while DU145 expressed all TLRs except TLR4, TLR7 and 9
Summary
Immune recognition of microorganisms is carried out by a set of receptors collectively referred to as pattern recognition receptors (PRR) These receptors are expressed by wide variety of immune cells and, as an essential part of innate immunity, are involved in immediate and direct recognition of molecular determinants specific to certain classes of pathogens [1]. Following TLR ligation, recruitment of MyD88 takes place which in turn associates with the intracellular domain of the TLR [15,16,17,18] leading to subsequent downstream activation of the nuclear factor, NF-kB, signaling pathway The latter is responsible for the initiation of pro-inflammatory responses characterized by the production of a vast array of chemokines and cytokines and in some cell populations by cell proliferation, as well [19]. The effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA), as well-known mediators of inflammation, on cancerous behavior of three prostate tumor cells, LNCaP, PC3 and DU145, were investigated
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