MicroRNAs in the control of metastatic bone disease

Abstract

Bone metastasis is a common and devastating complication of late-stage breast and prostate cancer. Complex interactions between tumor cells, bone cells, and a milieu of components in their microenvironment contribute to the osteolytic, osteoblastic, or mixed lesions present in patients with metastasis to bone. In the past decade microRNAs (miRNAs) have emerged as key players in cancer progression, but the importance of miRNAs in regulating cancer metastasis to bone is only now being appreciated. We emphasize here important concepts of bone biology and miRNAs in the context of breast and prostate cancer, and focus on recent advances that have improved our understanding of the role of specific miRNAs with direct involvement in metastatic bone disease.

Keywords: bone metastasis; breast cancer; miRNA; osteolytic/osteoblastic disease; prostate cancer.

Figure 1. Dysregulated miRNAs in breast and prostate cancer driving metastasis to bone

Illustrated are osteolytic lesions (characterized by bone degradation) and osteoblastic lesions (characterized by excessive bone formation). Breast cancer bone metastases are osteolytic in nature, whereas osteoblastic lesions occur most commonly in prostate cancer bone metastases; indeed, often a mixture of both lesions is present. Specific miRs are highlighted in the illustration, based on their recently documented functional role(s) in promoting osteolytic or osteoblastic metastatic bone disease in breast or prostate cancer, respectively. If the miR is reported to be up-regulated/aberrantly present in the disease state, it is shown in green. Conversely, if the miR is reported to be down-regulated/aberrantly absent in the disease state, it is shown in red. Black arrows indicate the stage of disease progression. The stages are depicted from primary tumor formation through the metastasis stage and resultant bone lesion, where aberrant expression of the miRNA has been shown to functionally promote bone metastatic disease. We refer the reader to the main text (“miRNAs driving bone metastasis”) as well as Table 1 for more detailed information on individual miRs depicted. Mets, metastasis; miR, microRNA.