Supplemental Figure 1: PC3 growth in bone does not increase ImP. PC3 tumor cells were injected into SCID mice 24 hours prior to implant with a wireless pressure monitoring device. A) A small increase in ImP during week 2 was observed, but was not statistically significant. B) Significant bone lysis due to tumor growth was observed. Tumor induced bone lysis may be a mechanism for relieving the pressure associated with more osteoblastic PCa tumors such as ACE1 and DU145.
ARTICLE ABSTRACTCross-talk between tumor cells and their microenvironment is critical for malignant progression. Cross-talk mediators, including soluble factors and direct cell contact, have been identified, but roles for the interaction of physical forces between tumor cells and the bone microenvironment have not been described. Here, we report preclinical evidence that tumor-generated pressure acts to modify the bone microenvironment to promote the growth of prostate cancer bone metastases. Tumors growing in mouse tibiae increased intraosseous pressure. Application of pressure to osteocytes, the main mechanotransducing cells in bone, induced prostate cancer growth and invasion. Mechanistic investigations revealed that this process was mediated in part by upregulation of CCL5 and matrix metalloproteinases in osteocytes. Our results defined the critical contribution of physical forces to tumor cell growth in the tumor microenvironment, and they identified osteocytes as a critical mediator in the bone metastatic niche. Cancer Res; 75(11); 2151–8. ©2015 AACR.