Promising research on treatments for virulent breast cancers

Bone sialoprotein (BSP), a major protein in bone and other mineralized tissue, has been the research focus for years of Dr. Q. Tu, a research scientist at Tufts Dental School. He was the first to demonstrate the presence of BSP auto-regulation in the earliest stages of bone formation. In fact, BSP, which is instrumental in mineralization of bone and tissue, is at its highest post-birth levels in the first two weeks of life when bones are continuing to develop. Those levels drop sharply after the first two weeks and thereafter are typically noticeable only in the regeneration of bone, for instance after a bone fracture.

One of the issues a team led by Dr. Tu is investigating is whether BSP may connect to breast cancer metastasis to bone. Dr. Tu’s interest in bone metastasis was sparked by a 1994 study by a group of Belgian scientists that found BSP in human breast cancer cells—an unexpected discovery because BSP was thought to be limited to bone and other mineralized tissue.

BSP also was found in prostate cancer cells. Both breast and prostate cancers are more likely than other cancers to spread to bone. Bone lesions caused by metastasis are found in 90 percent of people who die of breast cancer, and higher BSP levels in breast cancer cells correlate to higher metastasis and death rates.

Dr. Tu and his colleagues used a novel approach, involving transgenic mouse line and chicken embryos, to study in vivo the effect of BSP on 4T1 and human breast cancer cells’ ability to break into a blood vessel and metastasize preferentially to bone . They found BSP appeared to enhance that early step in metastasis, while the introduction of BSP antibodies hindered it.

Their most recent study focused on the role BSP might play in the “homing” of breast cancer cells to bone. The study, published in the International Journal of Oncology and JBMR, supported a strong role for BSP and perhaps, even more exciting, a strong anti-metastasis role for a BSP antibody.

The experiment involved injecting 40 mice, including cathepsin K-BSP transgeinic mice, with 4T1 breast cancer cells. One group of mice received cells with an over-expression of human BSP. The second group received cells that repressed BSP, and the third group had no extra BSP injected. Through four weeks observation, X-rays and Xenogen Imaging showed metastatic lesions on the leg bones of all of the mice in the first group with more rapid growth than the other two groups, three of the mice in the control group and only one of the mice in the repressed-BSP group. The research provide new insight into the mechanism by which breast cancer cells metastasize into mineraliized bone tissue, and a promising approach to treat virulent cancers.

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