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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 immunohistochemistry with tumor associated macrophages. (A) CD68 positive cells are demonstrated in the stroma adjacent to the prostate cancer epithelium (20×). (B) CD206 (mannose receptor) positive cells are shown in the stroma adjacent to the prostate cancer epithelium (20×). (C) Prostate cancer immunostained with anti-CCL2 (CCL2) showing epithelial and stromal cell expression (40×). (D) Prostate cancer immunostained showing nuclear and cytoplasmic NF-κB p65 (40×).
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Figure 8: Prostate immunohistochemistry with tumor associated macrophages. (A) CD68 positive cells are demonstrated in the stroma adjacent to the prostate cancer epithelium (20×). (B) CD206 (mannose receptor) positive cells are shown in the stroma adjacent to the prostate cancer epithelium (20×). (C) Prostate cancer immunostained with anti-CCL2 (CCL2) showing epithelial and stromal cell expression (40×). (D) Prostate cancer immunostained showing nuclear and cytoplasmic NF-κB p65 (40×).

Mentions: Prostate cancer tissues were immunostained to analyze prostate cancer macrophage, CCL2 and NF-κB subunit localization (Figure 8A-8D). Prostate sections contained CD68 and CD206 (macrophage mannose receptor) positive cells in the stroma (Figures 8A, 8B). The prostate cancer epithelium contained CCL2 positive cells (Figure 8C). NF-κBp65 was observed within the cytoplasm and nucleus of the prostate cancer epithelium (Figure 8D). The fraction of NF-κB positive cells ranged up to 70 percent. A representative section shows NF-κBp65 positive staining in 10 percent of the cancer cells (Figure 8D). The NF-κBp65 and c-Rel immunohistochemistry scores in cancer containing prostate tissues correlated with Gleason's score and were increased compared with biopsy samples containing benign epithelium (Figure 9).


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 immunohistochemistry with tumor associated macrophages. (A) CD68 positive cells are demonstrated in the stroma adjacent to the prostate cancer epithelium (20×). (B) CD206 (mannose receptor) positive cells are shown in the stroma adjacent to the prostate cancer epithelium (20×). (C) Prostate cancer immunostained with anti-CCL2 (CCL2) showing epithelial and stromal cell expression (40×). (D) Prostate cancer immunostained showing nuclear and cytoplasmic NF-κB p65 (40×).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4548876&req=5

Figure 8: Prostate immunohistochemistry with tumor associated macrophages. (A) CD68 positive cells are demonstrated in the stroma adjacent to the prostate cancer epithelium (20×). (B) CD206 (mannose receptor) positive cells are shown in the stroma adjacent to the prostate cancer epithelium (20×). (C) Prostate cancer immunostained with anti-CCL2 (CCL2) showing epithelial and stromal cell expression (40×). (D) Prostate cancer immunostained showing nuclear and cytoplasmic NF-κB p65 (40×).
Mentions: Prostate cancer tissues were immunostained to analyze prostate cancer macrophage, CCL2 and NF-κB subunit localization (Figure 8A-8D). Prostate sections contained CD68 and CD206 (macrophage mannose receptor) positive cells in the stroma (Figures 8A, 8B). The prostate cancer epithelium contained CCL2 positive cells (Figure 8C). NF-κBp65 was observed within the cytoplasm and nucleus of the prostate cancer epithelium (Figure 8D). The fraction of NF-κB positive cells ranged up to 70 percent. A representative section shows NF-κBp65 positive staining in 10 percent of the cancer cells (Figure 8D). The NF-κBp65 and c-Rel immunohistochemistry scores in cancer containing prostate tissues correlated with Gleason's score and were increased compared with biopsy samples containing benign epithelium (Figure 9).

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