BoneKEy Reports | BoneKEy Watch

Cathepsin B: could it prevent bone metastases from breast cancer?

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DOI:10.1038/bonekey.2012.77

The role of cathepsin B has been clarified using 4T1.2 cells in immunocompetent mice as a model of breast cancer metastasis. Withana et al. first demonstrated that the spontaneous bone metastases that developed in the model after injection of 4T1.2 cells into the fourth mammary fat pad closely mimicked human disease in terms of cathepsin B expression. Cathepsin B was present both in primary tumor cells, stromal cells and cells within the bone metastases.

The researchers then inhibited cathepsin B using a specific gene silencing RNA; this created stable cells expressing virtually no cathepsin B. When these were injected into the same type of mice in the same way, the mammary tumors grew as usual but lung and spine metastases were reduced quite dramatically.

Similarly, mice that had developed tumors after being injected with 4T1.2 cells developed fewer lung and bone metastatic tumors when treated with a specific cathepsin B inhibitor; in fact, these tumors were undetectable in many of the treated mice.

Editor's comment: Previous experimental studies have shown that cathepsin K inhibitors slow the progression of breast cancer bone metastases in animals by reducing osteoclast-mediated bone resorption. Here, Withana and colleagues show that a cathepsin B inhibitor targets both the tumor cells and stromal cells to reduce experimental bone metastases, thereby providing a better therapeutic benefit.

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