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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

Selected cytokine levels of PC-3 High Invasion cells, DU145 and U-937 and co-culture supernatants. The supernatant cytokine levels were assayed by ELISA after 48 hours culture. (A) Co-cultures of U-937 cells with PC-3 High Invasion or DU145 cells yield increased CCL2 levels compared with cancer cell or U-937 supernatants alone. (B) High Gro-alpha levels were detected in PC-3 cell cultures and were decreased in the co-cultures and not quite statistically different, P=0.0561. (C). High Interleukin-6 levels were detected in PC-3 High Invasion cell cultures and were not significantly different in the co-cultures. (D) PC-3 High Invasion cell cultures yielded high Interleukin-8 levels which were not significantly different in the co-cultures. DU-145 yielded low Gro-alpha, IL-6 and IL-8 levels. The data are expressed as mean ± SD of four independent experiments. *P<0.01, **P<0.001.
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Figure 3: Selected cytokine levels of PC-3 High Invasion cells, DU145 and U-937 and co-culture supernatants. The supernatant cytokine levels were assayed by ELISA after 48 hours culture. (A) Co-cultures of U-937 cells with PC-3 High Invasion or DU145 cells yield increased CCL2 levels compared with cancer cell or U-937 supernatants alone. (B) High Gro-alpha levels were detected in PC-3 cell cultures and were decreased in the co-cultures and not quite statistically different, P=0.0561. (C). High Interleukin-6 levels were detected in PC-3 High Invasion cell cultures and were not significantly different in the co-cultures. (D) PC-3 High Invasion cell cultures yielded high Interleukin-8 levels which were not significantly different in the co-cultures. DU-145 yielded low Gro-alpha, IL-6 and IL-8 levels. The data are expressed as mean ± SD of four independent experiments. *P<0.01, **P<0.001.

Mentions: CCL2 was measured at very low levels (<10 pg/mL) by enzyme-linked immunosorbent assays (ELISA) in prostate cancer cell supernatants and U-937 supernatants (147.5 ± 24 pg/mL)(Figure 3A). In the PC-3 High Invasive/U-937 and DU145/U-937 co-culture supernatants, CCL2 increased to 638 ± 17 pg/mL and 600 ± 45 pg/mL, respectively (Figure 3A). Similarly, in LNCaP/U-937 co-culture supernatants, CCL2 was increased from less than 10 pg/mL to 358 pg/mL (Figure 4A).


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)

Selected cytokine levels of PC-3 High Invasion cells, DU145 and U-937 and co-culture supernatants. The supernatant cytokine levels were assayed by ELISA after 48 hours culture. (A) Co-cultures of U-937 cells with PC-3 High Invasion or DU145 cells yield increased CCL2 levels compared with cancer cell or U-937 supernatants alone. (B) High Gro-alpha levels were detected in PC-3 cell cultures and were decreased in the co-cultures and not quite statistically different, P=0.0561. (C). High Interleukin-6 levels were detected in PC-3 High Invasion cell cultures and were not significantly different in the co-cultures. (D) PC-3 High Invasion cell cultures yielded high Interleukin-8 levels which were not significantly different in the co-cultures. DU-145 yielded low Gro-alpha, IL-6 and IL-8 levels. The data are expressed as mean ± SD of four independent experiments. *P<0.01, **P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Selected cytokine levels of PC-3 High Invasion cells, DU145 and U-937 and co-culture supernatants. The supernatant cytokine levels were assayed by ELISA after 48 hours culture. (A) Co-cultures of U-937 cells with PC-3 High Invasion or DU145 cells yield increased CCL2 levels compared with cancer cell or U-937 supernatants alone. (B) High Gro-alpha levels were detected in PC-3 cell cultures and were decreased in the co-cultures and not quite statistically different, P=0.0561. (C). High Interleukin-6 levels were detected in PC-3 High Invasion cell cultures and were not significantly different in the co-cultures. (D) PC-3 High Invasion cell cultures yielded high Interleukin-8 levels which were not significantly different in the co-cultures. DU-145 yielded low Gro-alpha, IL-6 and IL-8 levels. The data are expressed as mean ± SD of four independent experiments. *P<0.01, **P<0.001.
Mentions: CCL2 was measured at very low levels (<10 pg/mL) by enzyme-linked immunosorbent assays (ELISA) in prostate cancer cell supernatants and U-937 supernatants (147.5 ± 24 pg/mL)(Figure 3A). In the PC-3 High Invasive/U-937 and DU145/U-937 co-culture supernatants, CCL2 increased to 638 ± 17 pg/mL and 600 ± 45 pg/mL, respectively (Figure 3A). Similarly, in LNCaP/U-937 co-culture supernatants, CCL2 was increased from less than 10 pg/mL to 358 pg/mL (Figure 4A).

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