Prostate cancer is frequently associated with bone metastases, where the crosstalk between tumor cells and key cells of the bone microenvironment (osteoblasts, osteoclasts, immune cells) amplifies tumor growth.
We have explored the potential of a novel cytokine, interleukin-27 (IL-27), for inhibiting this malignant crosstalk, and have examined the effect of autocrine IL-27 on prostate cancer cell gene expression, as well as the effect of paracrine IL-27 on gene expression in bone and T cells. In prostate tumor cells, IL-27 upregulated genes related to its signaling pathway while downregulating malignancy-related receptors and cytokine genes involved in gp130 signaling, as well as several protease genes. In both undifferentiated and differentiated osteoblasts, IL-27 modulated upregulation of genes related to its own signaling pathway as well as pro-osteogenic genes. In osteoclasts, IL27 downregulated several genes typically involved in malignancy and also downregulated osteoclastogenesis-related genes. Furthermore, an osteogenesis-focused real-time PCR array revealed a more extensive profile of pro-osteogenic gene changes in both osteoblasts and osteoclasts. In T lymphocyte cells, IL27 upregulated several activation-related genes and also genes related to the IL27 signaling pathway and downregulated several genes that could modulate osteoclastogenesis. Overall, our results suggest that IL-27 may be able to modify interactions between prostate tumor and bone microenvironment cells and thus could be used as a multifunctional therapeutic for restoring bone homeostasis while treating metastatic prostate tumors.
Written by:
Zolochevska O, Diaz-Quiñones AO, Ellis J, Figueiredo ML. Are you the author?
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77555.
Reference: J Cell Physiol. 2012 Oct 19. Epub ahead of print.
doi: 10.1002/jcp.24265
PubMed Abstract
PMID: 23086758
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