Mechanisms of tumor metastasis to the bone: challenges and opportunities

In human cancers, bone is a common site for metastasis. It is well known that metastasis is the cause of morbidity and mortality in patients with cancer. Both breast and prostate carcinomas have a propensity to metastasize to bone. In general, metastatic breast cancers result in osteolytic lesions. On the other hand, prostate cancer metastases are osteoblastic and result in osteosclerosis. Thus, bone formation and bone resorption are at the crux of the cancer metastasis problem. For example, in the prostate, there is a vicious cycle of metastasis to bone (Fig. 1). Metastases to bone causes excruciating bone pain, pathological fractures, and eventually death, and therefore is a serious challenge to both bone biologists and cancer cell biologists. The stromal-epithelial interactions in breast and prostate are critical in initiation of carcinogenesis and the progression of the metastatic cascade to bone (Fig. 2). Over a hundred years ago, Stephen Paget enunciated the seed and soil hypothesis in which seeds of metastatic cancer cells of breast preferentially settle in the soil of bone matrix. Thus, the prostate/breast cancer bone interface and continuum has continuously presented challenges and opportunities and were discussed at a recent workshop.