Lindholm Paul F, Sivapurapu Neela, Jovanovic Borko, Kajdacsy-Balla André
Department of Pathology, Northwestern University, The Feinberg School of Medicine, Chicago, USA.
Indigenèse Biotechnologies, Hyderabad, India.
J Clin Cell Immunol. 2015 Apr;6(2). doi: 10.4172/2155-9899.1000308.
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.
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.
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.
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.
肿瘤微环境中含有可影响癌症生长和进展的炎性细胞；然而，这些效应的介质因癌症类型而异。前列腺癌细胞与单核细胞相互作用促进癌症进展的机制尚未完全明确。本研究检测了导致前列腺癌细胞侵袭增加的前列腺癌细胞与单核细胞的相互作用。
我们分析了共培养体系中前列腺癌细胞与单核细胞系细胞相互作用时的前列腺癌细胞侵袭、核因子κB（NF-κB）活性及细胞因子表达情况。检测了单核细胞趋化因子（MCP-1/CCL2）和NF-κB活性在共培养诱导的前列腺癌侵袭中的作用。采用免疫组织化学方法分析临床前列腺癌中NF-κB的表达。
在前列腺癌细胞系与单核细胞系细胞的共培养体系中，与单独培养的单核细胞或癌细胞相比，（C-C基序）配体2（CCL2）水平显著升高。重组CCL2以剂量依赖性方式诱导前列腺癌细胞侵袭，类似于与单核细胞的共培养。CCL2中和抗体和CCR2抑制剂RS102895可抑制单核细胞诱导的前列腺癌细胞侵袭。蛋白酶体抑制剂Lactacystin和NF-κB抑制剂Bay11-7082可抑制共培养体系中诱导的前列腺癌细胞侵袭和CCL2表达。前列腺癌细胞NF-κB DNA结合活性取决于CCL2剂量，并被CCL2中和抗体抑制。临床前列腺癌NF-κB表达与肿瘤分级相关。
与单核细胞系细胞系共培养通过增加CCL2表达和提高前列腺癌细胞NF-κB活性刺激前列腺癌细胞侵袭增加。CCL2和NF-κB可能是干预炎症诱导的前列腺癌侵袭的有用治疗靶点。
