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Metastasis to bone or lung? Peroxiredoxin-2 expression may be the key
DOI:10.1038/bonekey.2012.106
Cancer cells metastasizing to lung tissue are subjected to an aerobic environment where they are susceptible to attack by reactive oxygen species (ROS); cells colonizing bone tissue are far less exposed to ROS damage. Stresing et al., having noted the upregulation of peroxiredoxins and other antioxidant proteins in lung tissue, compared how peroxiredoxin-2 (PRDX2) expression affected metastasis of breast cancer cells to bone versus lung tissue.
Breast cancer cells of variant MDA-MB-435, which spread mainly to lung tissue, had their PRDX2 gene silenced by transduction with short hairpin RNAs, while MDA-MB-231 cells, which metastasize to bone tissue, were induced to overexpress PRDX2.
MDA-MB-435 cells with the silenced PRDX2 showed higher sensitivity to oxidative stress than their parent cells and their growth in lung tissue was significantly inhibited. In bone, overexpression of PRDX2 also had a profound impact, with skeletal tumor burden and the level of bone destruction much reduced. The authors suggest that breast cancer cells that express high levels of PRDX2 may preferentially metastasize to lung tissue rather than bone; this gene may therefore be useful as a prognostic marker, and could be a potential therapeutic target in both bone and lung metastasis.
Editor's comment: This study provides compelling evidence that breast cancer cells metastasizing to lungs, but not to bones, have to adapt and protect themselves against oxidative stress in the pulmonary microenvironment.
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