BoneKEy Reports | BoneKEy Watch
Coco expression in lung promotes organ-specific metastasis
DOI:10.1038/bonekey.2012.219
Understanding the mechanisms of dormancy in breast cancer has important clinical implications for controlling disease progression. Here, Gao et al. designed a gain-of-function cDNA screening protocol to check known mammary carcinoma cell lines that have become ‘stuck’ at well-defined stages of the process of metastasis. This allowed them to identify genes that could be potential mediators of metastasis.
The results suggested that the metastatic capability present in different cell lines closely correlated with expression of Coco, a secreted TGF-β ligand inhibitor. Co-injection of Coco with cells that do not normally establish macrometastases resulted in efficient lung metastasis, while silencing Coco in highly metastatic cells resulted in significantly reduced lung colonization.
The mechanisms involved are complex, but Coco seems to block bone morphogenetic protein (BMP) ligands that are present in lung tissue; although Coco expression correlates with lung metastasis, it does not affect metastasis to other sites such as the brain or bone, which may contain niches that do not have bioactive BMP.
Editor’s comment: Previous studies have shown that tumor-derived vascular cell adhesion molecule 1 (VCAM-1) promotes the outgrowth of dormant human breast cancer cells in bone. Gao and colleagues now provide strong evidence that Coco induces dormant breast cancer cells to undergo reactivation in the lung, but not in the bone or brain. Taken together, these findings reveal the existence of organ-specific molecules that can overcome metastatic dormancy and allow reactivation to overt metastasis.
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