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Nakajima et al. Galectin-3 helps drive bone metastasis of prostate and breast cancers



DOI:10.1038/bonekey.2016.89

Galectin-3 (Gal-3) is a member of the lectin family of proteins that is involved in a range of intracellular and extracellular interactions. It has been implicated in bone metastasis of breast and prostate cancer and in this study, Nakajima et al. explore how Gal-3 interacts with osteocytes in the microenvironment of the bone marrow to promote bone destruction.

Having shown that Gal-3-positive cells were found near mature osteoclasts in osteosarcoma, the researchers demonstrated that suppression of Gal-3 led to a reduction in osteoclast maturation, and a fall in the level of osteoclast differentiation markers, such as tartrate-resistant acid phosphatase. They also identified a short amino acid sequence in the portion of Gal-3 that is key to its impact on osteoclastogenesis.

Gal-3 was also detected in culture media from breast and prostate cancer cell lines. The cleaved form was predominant in prostate cancer metastases while the intact form was found at higher levels in breast cancer metastases. This is important because intact Gal-3 interacts with myosin-2A on the osteoclast surface, stimulating differentiation, while the cleaved form does not.

Editor’s comment: The authors provide evidence for a novel mechanism underlying breast cancer osteolytic lesions in which cancer-secreted Gal-3 enhances osteoclast fusion. They further suggest that Gal-3 is a potential therapeutic target and that strategies to block its effect on osteoclasts could delay or prevent cancer-associated bone destruction.


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