The same and not the same: heterogeneous functional activation of prostate tumor cells by TLR ligation

Cancer Cell International

Amir-Hassan Zarnani²  Leila Katouzian³  Omid Zarei⁵  Jamileh Ghasemi⁴  Saeed Zarei⁷  Ebrahim Mirzadegan³  Nesa Rashidi¹  Noor Amirmozaffari⁶  Simin Rezania⁸ 

[1] Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran;Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran;Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran;Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran;Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran;Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran;Biophysics Institute, Medical University of Graz, Graz, Austria

关键词: Inflammation;    Adhesion;    Invasion;    Pro-inflammatory cytokine;    Proliferation;    Prostate cancer;    Toll like receptor;   

Others  :  791800
DOI  :  10.1186/1475-2867-14-54

 received in 2014-01-14, accepted in 2014-05-29,  发布年份 2014

【 摘 要 】

Background

Many 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.

Methods

Expression 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.

Results

We 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.

Conclusion

The 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.

【 授权许可】

   
2014 Rezania et al.; licensee BioMed Central Ltd.

【 图 表 】

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