Introduction and objective: Inflammation plays a key role in the etiology of carcinoma of colon, cervix or liver, but PCa, in which inflammation has not been deemed to play a causative role, also display a pro-inflammatory gene profile. NF-κB is central to the induction of inflammation and the classical and alternative NF-κB activation pathways have been shown to modulate expression of inflammatory mediators. Here we explored the induction of markers of tumor-infiltrating inflammatory cells in two in vivo models overexpressing NF-κB2/p52.

Methods: LNCaP human PCa cells were infected with adenoviruses encoding empty vector or NF-κB2/p52 and injected s.c. into both flanks of nude mice. Gene expression of markers of inflammatory mediators such as macrophages, lymphocytes and dendritic cells was analyzed in the tumor tissues by qRT-PCR. In addition, whole prostates were collected from transgenic mice expressing NF-κB2/p52 in the prostate and RNA was analyzed for inflammatory markers. Expression of the cell surface markers was validated by immunohistochemistry in sections of whole prostates.

Results: The infiltration of host immune cells into the xenograft tissues was detected by expression of surface markers of cells of myeloid and lymphoid lineage. The expression of B220 (B cells), F4/80 (activated macrophages), Cd8A (CTL) was increased in p52-expressing xenografts compared to controls, indicating the presence of host-derived inflammatory cells in the xenografts. Expression levels of chemokines (Cxcl1), chemokine receptors (Ccr1, Ccr3) and pro-inflammatory cytokines (Il-6 and Tnf) were enhanced in the xenografts compared to the controls, indicating that expression of NF-κB2/p52 induces an inflammatory response in xenografts of human PCa cells.

Compared to littermate negative controls, expression of B220, F4/80, Cd8A and Cd208 was increased in transgenic mouse prostates expressing p52. Furthermore, expression levels of Cxcl1, Ccr1, Ccr3, Il-6 and Tnf were also enhanced compared to controls, indicating the induction of inflammation in mouse prostates by NF-κB2/p52.

Conclusions: Our previous studies have shown that NF-κB2/p52 plays an important role in the development of castration resistance in human PCa cells. In this study we showed that NF-κB2/p52 may induce an inflammatory response in xenografts of human PCa cells or in transgenic mouse prostates, and thereby promote tumor proliferation.

Citation Format: Nagalakshmi Nadiminty, Ramakumar Tummala, Wei Lou, Christopher P. Evans, Allen C. Gao. NF-κB2/p52 induces expression of inflammatory mediators in prostate cancer in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3116. doi:10.1158/1538-7445.AM2013-3116

©2013 American Association for Cancer Research
2013