Bone sialoprotein-αvβ3 integrin axis promotes breast cancer metastasis to the bone

The underlying mechanisms of breast cancer cells metastasizing to distant sites are complex and multifactorial. Bone sialoprotein (BSP) and alpha v beta 3 integrin were reported to promote the metastatic progress of breast cancer cells, particularly metastasis to bone. Most theories presume that BSP promotes breast cancer metastasis by binding to alpha v beta 3 integrin. Interestingly, we found the alpha v beta 3 integrin decreased in BSP silenced cells (BSPi), which have weak ability to form bone metastases. However, the relevance of their expression in primary tumor and the way they participate in metastasis are not clear. In this study, we evaluated the relationship between BSP, alpha v beta 3 integrin levels, and the bone metastatic ability of breast cancer cells in patient tissues, and the data indicated that the alpha v beta 3 integrin level is closely correlated to BSP level and metastatic potential. Overexpression of alpha v beta 3 integrin in cancer cells could reverse the effect of BSPi in vitro and promote bone metastasis in a mouse model, whereas knockdown of alpha v beta 3 integrin have effects just like BSPi. Moreover, The Cancer Genome Atlas data and RT-PCR analysis have also shown that SPP1, KCNK2, and PTK2B might be involved in this process. Thus, we propose that alpha v beta 3 integrin is one of the downstream factors regulated by BSP in the breast cancer-bone metastatic cascade.