PTGS2 and breast carcinoma: Since both IL-11 and IL-8 as produced by both osteoblasts [50,193] and breast cancer cells [177,197] have been shown to stimulate osteoclastogenesis both by RANK-L dependent and independent mechanisms [176,177,197,221], a system favoring increased COX2 expression would lead to increased osteolytic metastases and thus further drive the ‘vicious cycle’ of breast cancer bone metastases.