The anti-metastatic micro-environment of the bone: Importance of osteocyte Cx43 hemichannels

Bone metastases of tumor cells are a common and life-threatening feature of a variety of late-stage cancers, including breast cancers. However, until now, much less has been known about the intrinsic anti-metastatic properties of the bones and how these could be exploited to prevent or treat bone metastases. Very recently, native Cx43 hemichannels present in osteocytes have been identified as important anti-metastatic signaling complexes by establishing high local extracellular ATP levels. Moreover, bisphosphonate drugs, applied as adjuvant therapies in the treatment of breast cancer patients and bone diseases, are known to display anti-metastatic properties. Now, it became clear that these compounds exert their effects through osteocyte Cx43 hemichannels, thereby triggering their opening and promoting ATP release in the extracellular micro-environment. Hence, endogenous osteocyte Cx43 hemichannels emerge as important and promising therapeutic targets for the prevention of bone metastases and/or clinical treatment of bone-metastasized breast cancers. (C) 2016 Elsevier B.V. All rights reserved.