IBMS BoneKEy | BoneKEy Watch
ALCAM expression in prostate cancer cells promotes bone metastases
DOI:10.1038/bonekey.2014.77
This study focused on the role of the activated leukocyte cell adhesion molecule (ALCAM) on metastatic progression of prostate cancer to bone.
Analysis of publicly available microarray datasets confirmed that high levels of ALCAM in patients with prostate cancer were associated with a greater risk of bone metastases and a less favorable outcome. Transforming growth factor beta (TGFβ), a known driver of bone metastasis in prostate cancer, was shown to induce expression of ALCAM and to promote its shedding from prostate cancer cells in vitro.
Shedding of ALCAM was shown to occur in vivo; the molecule has a half-life of 17 hours. Its presence in the blood corresponded to the presence of malignant, metastatic prostate tumours in mice. Shedding of ALCAM from tumour cells in vivo and in vitro was mediated by the enzyme ADAM metallopeptidase domain 17 (ADAM17).
Immunocompromised mice injected with metastatic prostate cancer cells with a knockdown of ALCAM developed a similar prostate tumour as mice without the ALCAM knockdown, but metastasis to skeletal tissue was significantly reduced. ALCAM expression appeared to promote survival and proliferation of prostate cancer cells in the bone microenvironment.
Editor’s comment: Hansen and colleagues provide strong evidence that ALCAM expression in prostate cancer cells not only contributes to the formation of experimental bone metastases, it also serves as a biomarker that predicts poor clinical outcome.
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