Prostate cancer cells undergoing ER stress in vitro and in vivo activate transcription of pro-inflammatory cytokines

Abstract

Navin R Mahadevan, Antonio Fernandez, Jeffrey J Rodvold, Gonzalo Almanza, Maurizio ZanettiThe Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, USABackground: Several micro-environmental and cell-intrinsic stimuli cause tumor cells to undergo endoplasmic reticulum (ER) stress in vivo. The occurrence of an ER stress response has been associated with tumor progression and angiogenesis. Recently, we found that pharmacological induction of ER stress in B lymphoma cells upregulates the transcription of several pro-inflammatory cytokines.Results: Here, we show that transgenic adenocarcinoma of the mouse prostate (TRAMP) C1 murine prostate cancer cells induced to undergo ER stress in vitro activate the transcription of interleukin 6 (IL-6), interleukin 23p19 (IL-23p19), and tumor necrosis factor a (TNF-a). Furthermore we show that TRAMP C1 tumors growing in vivo spontaneously experience ER stress and that transcription of IL-6, IL-23p19, and TNF-a correlates with the in vivo ER stress response.Conclusions: These results suggest that an ER stress response in prostate cancer cells activates a program of pro-inflammatory cytokine transcription. A possible implication of this finding is that cancer cells may use the ER stress response to modify their microenvironment.Keywords: unfolded protein response, tumorigenesis, inflammation