BoneKEy Reports | BoneKEy Watch
Breast cancer likely to metastasise to bone if RANK expression high
DOI:10.1038/bonekey.2012.134
Signaling through the receptor activator of NF-κB (RANK) is known to stimulate migration and metastasis of breast cancer to bone; a possible explanatory mechanism is put forward in this study by Palafox et al. Cell culture studies involving serial passages of human mammary epithelial cells overexpressing RANK demonstrated significant epithelial to mesenchymal transition (EMT); the cells also started to express stem cell markers and to take on stem cell properties, with the population of CD44+ and CD24 cells both increasing.
In breast cancer cell lines that lacked the BRCA1 gene, RANK overexpression made the cells more likely to become established tumors, and cells exhibited markers and behavior that made them more likely to migrate and metastasize.
Finally, cells derived from human breast adenocarcinomas were analyzed for their expression levels of RANK. Significantly higher levels of RANK mRNA were found in cells from aggressive triple negative tumors, and from tumors with a high proliferation index or histological grade.
Editor's comment: This study provides compelling evidence that overexpression of RANK in mammary epithelial cells causes transformation and imbues the cells with the properties of cancer stem cells. The finding helps to explain why high RANK expression in primary breast tumors is associated with such a poor prognosis, with a high rate of bone metastasis.
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