Targeting IL-6 and RANKL signaling inhibits prostate cancer growth in bone.

In prostate cancer metastases to bone, cancer cell-derived cytokines stimulate RANKL expression by cells of the osteoblast lineage, which in turn activates osteoclastic bone resorption. However, it is unclear whether cells of the osteoblast lineage signal back to prostate cancer cells, and if so, whether such direct cross-talk can be targeted therapeutically. Using the human prostate cancer cell line, PC3, we identified two novel signalling pathways acting between cells of the osteoblast lineage and cancer cells.

Direct crosstalk between cancer and osteoblast lineage cells fuels metastatic growth in bone via auto-amplification of IL-6 and RANKL signaling pathways.

The bone microenvironment and its modification by cancer and host cell interactions is a key driver of skeletal metastatic growth. Interleukin-6 (IL-6) stimulates receptor activator of NF-κB ligand (RANKL) expression in bone cells, and serum IL-6 levels are associated with poor clinical outcomes in cancer patients. We investigated the effects of RANKL on cancer cells and the role of tumor-derived IL-6 within the bone microenvironment.