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Zhou et al. Cx43 hemichannels in osteocytes and breast cancer metastasis
DOI:10.1038/bonekey.2016.53
Zhou et al. investigated the role of Cx43 hemichannels in osteocytes, revealing that opening these channels using bisphosphonates (zoledronic acid and alendronate) inhibits the ability of human breast cancer cells to grow, migrate and invade bone tissue.
Use of Cx43(E2), an antibody that blocks Cx43 hemichannels and prevents them opening, reduced the inhibitory effect observed. A similar inhibitory effect resulting from mechanical stimulation was also attenuated by Cx43(E2) treatment.
Further evidence that Cx43 could be a worthwhile therapeutic target came from studies on mice with a specific Cx43 osteocyte specific knockout and from transgenic mice with osteocytes in which the Cx43 gap junctions were impaired. Induced tumors grew faster and were more aggressive in both sets of mice and the inhibitory effect of zoledronic acid was significantly reduced. Interestingly though, tumor growth in transgenic mice which lacked gap junctions but still had functioning Cx43 hemichannels was indistinguishable from controls.
The authors conclude that their in vitro and in vivo studies demonstrate that Cx43 hemichannels are intrinsically protective against breast cancer metastasis, something that has potentially far-reaching clinical implications.
Editor’s comment: This study provides strong experimental evidence that activation of Cx43 hemichannels in osteocytes limits breast cancer growth in the skeleton. This study opens a new therapeutic avenue for the treatment of breast cancer bone metastasis.
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