BoneKEy Reports | BoneKEy Watch
A microRNA regulon inhibits metastasis of breast cancer to bone
DOI:10.1038/bonekey.2012.34
MicroRNAs are small, non-coding RNAs that post-transcriptionally control the translation and stability of functional messenger RNA. Loss of tumour-suppressive microRNAs from a cancer cell results in enhanced expression of target oncogenes, promoting tumour growth and metastasis to lung and bone.
A study by Png et al identifies miR-126, a microRNA that suppresses metastatic recruitment by endothelial cells in bone and lung tissue, and also inhibits metastatic angiogenesis and colonization. It acts by targeting three novel pro-angiogenic genes and biomarkers of human metastasis; MERTK, IGFBP2 and PITPNC1, albeit through different signalling pathways.
The hypothesis that the suppressive effect of miR-126 on metastasis is secondary to compromised endothelial cell recruitment was tested by injecting breast cancer cells over-expressing miR-126 together with endothelial cells into the portal circulation of immunodeficient mice. miR-126 cells alone strongly suppressed metastatic colonization of the liver, but the combination of miR-126 cells and endothelial cells resulted in significant liver metastasis.
Editor's comment: The pathways through which miR-126 acts to suppress cancer-mediated endothelial recruitment and subsequent metastatic colonization of bone tissue indicate that endothelial cells promote metastatic initiation. This may provide new therapies to prevent breast cancer from spreading to bone.
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