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Monocyte-Induced Prostate Cancer Cell Invasion is Mediated by Chemokine ligand 2 and Nuclear Factor-κB Activity.

Lindholm PF, Sivapurapu N, Jovanovic B, Kajdacsy-Balla A - J Clin Cell Immunol (2015)

Bottom Line: Prostate cancer cell invasion and CCL2 expression induced in the co-cultures was inhibited by Lactacystin and Bay11-7082 NF-κB inhibitors.Prostate cancer cell NF-κB DNA binding activity depended on CCL2 dose and was inhibited by CCL2 neutralizing antibodies.CCL2 and NF-κB may be useful therapeutic targets to interfere with inflammation-induced prostate cancer invasion.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Northwestern University, The Feinberg School of Medicine, Chicago, USA.

ABSTRACT

Study background: The tumor microenvironment contains inflammatory cells which can influence cancer growth and progression; however the mediators of these effects vary with different cancer types. The mechanisms by which prostate cancer cells communicate with monocytes to promote cancer progression are incompletely understood. This study tested prostate cancer cell and monocyte interactions that lead to increased prostate cancer cell invasion.

Methods: We analyzed the prostate cancer cell invasion and NF-κB activity and cytokine expression during interaction with monocyte-lineage cells in co-cultures. The roles of monocyte chemotactic factor (MCP-1/CCL2) and NF-κB activity for co-culture induced prostate cancer invasion were tested. Clinical prostate cancer NF-κB expression was analyzed by immunohistochemistry.

Results: In co-cultures of prostate cancer cell lines with monocyte-lineage cells, (C-C motif) ligand 2 (CCL2) levels were significantly increased when compared with monocytes or cancer cells cultured alone. Prostate cancer cell invasion was induced by recombinant CCL2 in a dose dependent manner, similar to co-cultures with monocytes. The monocyte-induced prostate cancer cell invasion was inhibited by CCL2 neutralizing antibodies and by the CCR2 inhibitor, RS102895. Prostate cancer cell invasion and CCL2 expression induced in the co-cultures was inhibited by Lactacystin and Bay11-7082 NF-κB inhibitors. Prostate cancer cell NF-κB DNA binding activity depended on CCL2 dose and was inhibited by CCL2 neutralizing antibodies. Clinical prostate cancer NF-κB expression correlated with tumor grade.

Conclusions: Co-cultures with monocyte-lineage cell lines stimulated increased prostate cancer cell invasion through increased CCL2 expression and increased prostate cancer cell NF-κB activity. CCL2 and NF-κB may be useful therapeutic targets to interfere with inflammation-induced prostate cancer invasion.

No MeSH data available.


Related in: MedlinePlus

Prostate cancer cell invasion and NF-κB activity in co-cultures. (A) The percent nuclear NF-κB was significantly induced in PC-3 High Invasive prostate cancer cells co-cultured with U-937 monocytes versus alone. (B) Relative PC-3 invasion in co-culture with U-937 cells was reduced from 196 ± 7 to 151 ± 12 percent by transfection with dominant negative IκBαS32/36A versus control vector. (C) Dose dependent nuclear NF-κB DNA binding activity was induced in PC-3 High Invasive cells following incubation with recombinant human CCL2 for 24 hours. (D) The CCL2 induced PC-3 High Invasive cell NF-κB activity was reduced when the cells were treated with anti-CCL2 neutralizing antibodies. The data are expressed as the mean ± SD of three independent experiments. *P<0.05, **P<0.01.
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Figure 7: Prostate cancer cell invasion and NF-κB activity in co-cultures. (A) The percent nuclear NF-κB was significantly induced in PC-3 High Invasive prostate cancer cells co-cultured with U-937 monocytes versus alone. (B) Relative PC-3 invasion in co-culture with U-937 cells was reduced from 196 ± 7 to 151 ± 12 percent by transfection with dominant negative IκBαS32/36A versus control vector. (C) Dose dependent nuclear NF-κB DNA binding activity was induced in PC-3 High Invasive cells following incubation with recombinant human CCL2 for 24 hours. (D) The CCL2 induced PC-3 High Invasive cell NF-κB activity was reduced when the cells were treated with anti-CCL2 neutralizing antibodies. The data are expressed as the mean ± SD of three independent experiments. *P<0.05, **P<0.01.

Mentions: PC-3 High Invasive prostate cancer cells co-cultured with U-937 cells showed increased nuclear NF-κB p65 compared with PC-3 cancer cells cultured alone (Figure7A). PC-3 transfection with IκBαS32/36A inhibited PC-3 invasion in the co-cultures when compared with control vector transfected PC-3 cells (Figure 7B). Transfection of the PC-3 cells with dominant negative IκBα S32/36A expression vector inhibited NF-κB-Luciferase reporter and NF-κB DNA binding activity compared with controls (Supplementary Figure 1).


Monocyte-Induced Prostate Cancer Cell Invasion is Mediated by Chemokine ligand 2 and Nuclear Factor-κB Activity.

Lindholm PF, Sivapurapu N, Jovanovic B, Kajdacsy-Balla A - J Clin Cell Immunol (2015)

Prostate cancer cell invasion and NF-κB activity in co-cultures. (A) The percent nuclear NF-κB was significantly induced in PC-3 High Invasive prostate cancer cells co-cultured with U-937 monocytes versus alone. (B) Relative PC-3 invasion in co-culture with U-937 cells was reduced from 196 ± 7 to 151 ± 12 percent by transfection with dominant negative IκBαS32/36A versus control vector. (C) Dose dependent nuclear NF-κB DNA binding activity was induced in PC-3 High Invasive cells following incubation with recombinant human CCL2 for 24 hours. (D) The CCL2 induced PC-3 High Invasive cell NF-κB activity was reduced when the cells were treated with anti-CCL2 neutralizing antibodies. The data are expressed as the mean ± SD of three independent experiments. *P<0.05, **P<0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4548876&req=5

Figure 7: Prostate cancer cell invasion and NF-κB activity in co-cultures. (A) The percent nuclear NF-κB was significantly induced in PC-3 High Invasive prostate cancer cells co-cultured with U-937 monocytes versus alone. (B) Relative PC-3 invasion in co-culture with U-937 cells was reduced from 196 ± 7 to 151 ± 12 percent by transfection with dominant negative IκBαS32/36A versus control vector. (C) Dose dependent nuclear NF-κB DNA binding activity was induced in PC-3 High Invasive cells following incubation with recombinant human CCL2 for 24 hours. (D) The CCL2 induced PC-3 High Invasive cell NF-κB activity was reduced when the cells were treated with anti-CCL2 neutralizing antibodies. The data are expressed as the mean ± SD of three independent experiments. *P<0.05, **P<0.01.
Mentions: PC-3 High Invasive prostate cancer cells co-cultured with U-937 cells showed increased nuclear NF-κB p65 compared with PC-3 cancer cells cultured alone (Figure7A). PC-3 transfection with IκBαS32/36A inhibited PC-3 invasion in the co-cultures when compared with control vector transfected PC-3 cells (Figure 7B). Transfection of the PC-3 cells with dominant negative IκBα S32/36A expression vector inhibited NF-κB-Luciferase reporter and NF-κB DNA binding activity compared with controls (Supplementary Figure 1).

Bottom Line: Prostate cancer cell invasion and CCL2 expression induced in the co-cultures was inhibited by Lactacystin and Bay11-7082 NF-κB inhibitors.Prostate cancer cell NF-κB DNA binding activity depended on CCL2 dose and was inhibited by CCL2 neutralizing antibodies.CCL2 and NF-κB may be useful therapeutic targets to interfere with inflammation-induced prostate cancer invasion.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Northwestern University, The Feinberg School of Medicine, Chicago, USA.

ABSTRACT

Study background: The tumor microenvironment contains inflammatory cells which can influence cancer growth and progression; however the mediators of these effects vary with different cancer types. The mechanisms by which prostate cancer cells communicate with monocytes to promote cancer progression are incompletely understood. This study tested prostate cancer cell and monocyte interactions that lead to increased prostate cancer cell invasion.

Methods: We analyzed the prostate cancer cell invasion and NF-κB activity and cytokine expression during interaction with monocyte-lineage cells in co-cultures. The roles of monocyte chemotactic factor (MCP-1/CCL2) and NF-κB activity for co-culture induced prostate cancer invasion were tested. Clinical prostate cancer NF-κB expression was analyzed by immunohistochemistry.

Results: In co-cultures of prostate cancer cell lines with monocyte-lineage cells, (C-C motif) ligand 2 (CCL2) levels were significantly increased when compared with monocytes or cancer cells cultured alone. Prostate cancer cell invasion was induced by recombinant CCL2 in a dose dependent manner, similar to co-cultures with monocytes. The monocyte-induced prostate cancer cell invasion was inhibited by CCL2 neutralizing antibodies and by the CCR2 inhibitor, RS102895. Prostate cancer cell invasion and CCL2 expression induced in the co-cultures was inhibited by Lactacystin and Bay11-7082 NF-κB inhibitors. Prostate cancer cell NF-κB DNA binding activity depended on CCL2 dose and was inhibited by CCL2 neutralizing antibodies. Clinical prostate cancer NF-κB expression correlated with tumor grade.

Conclusions: Co-cultures with monocyte-lineage cell lines stimulated increased prostate cancer cell invasion through increased CCL2 expression and increased prostate cancer cell NF-κB activity. CCL2 and NF-κB may be useful therapeutic targets to interfere with inflammation-induced prostate cancer invasion.

No MeSH data available.


Related in: MedlinePlus