IBMS BoneKEy | BoneKEy Watch
The integrin αvβ6 promotes metastasis of prostate cancer cells to bone
DOI:10.1038/bonekey.2014.76
Dutta et al. explored the role of integrin signaling in prostate cancer metastasis. Analysis of human prostate cancer cells from patients with bone metastases revealed expression of the integrin αvβ6 in 22 out of 23 specimens; the integrin was functionally active.
When immunocompromised mice had cells expressing αvβ6 injected into their tibial medullar cavity, extensive osteolysis was observed in vivo. All trabecular bone disappeared from the injection site and there was significant erosion of cortical bone, allowing the tumour to invade nearby muscle tissue. Osteolysis did not occur in mice injected with cells expressing αvβ5.
Cells expressing αvβ6 demonstrated upregulation of matrix metalloproteinase 2 (MMP2) and parathyroid hormone-related protein (PTHrP). Expression of αvβ6 and MMP2 in prostate cancer cells were directly correlated and the authors suggest that MMP2 promotes osteolysis by αvβ6 by degrading the bone matrix. The effect of αvβ6 on MMP2 was independent of any interaction with the androgen receptor in prostate cancer cells.
Editor’s comment: McCabe et al. previously reported that integrin αvβ3 promotes the formation of osteoblastic lesions in animal models of prostate cancer bone metastasis. Taken together, these results highlight specific bone-related functions of tumor integrin αvβ3 and αvβ6 in the development of prostate cancer bone metastases. Strategies that target these two integrins might, therefore, translate into improved therapies to delay skeletal lesions associated with advanced prostate cancer.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.