Scientists block breast cancer cells from hiding in bones of mice, prompting hope for human trials
Published 30 May 2016
Scientists have successfully blocked breast cancer cells from entering and hiding in the bones of mice, where they can survive chemotherapy treatment.
Researchers at Duke University have also devised a method of flushing breast cancer cells out of bone marrow in mice, making them easier to eradicate through conventional treatments or by the immune system.
The findings, published in the journal Science Translational Medicine, heralds the prospect of similar practices being trialled in humans and has prompted hopes that one of the most devastating characteristics of breast cancer can be prevented.
Most often, the site of the metastasized cancer is in the bone - now we know how they are getting in
For many patients, breast cancer can return years after therapy and spread to other parts of the body.
Previous research suggests that bone marrow may offer a safe haven from chemotherapy, meaning breast cancer cells can lie dormant for an extended period of time.
Up to now, however, little has been known about how metastatic breast cancer cells enter and hide in bones.
Using real-time microscopy techniques, the Duke University Team tracked the migration of breast cancer cells through the bone marrow of mice and identified E-selectin, the protein that allows cancer cells to enter the bone barrow, and CXCR4, the protein that anchors them to the bone and allows them to hide.
Treating the mice with an E-selectin inhibitor blocked breast cancer cells from entering the bone, and a CXCR4 inhibitor forced them back out into the bloodstream.
Dorothy Sipkins, Associate Professor at Duke, said: “Clinical studies have found that breast cancer can be caught early and treated, and patients can have no signs of disease.
“Then five, 10 or even 15 years later, a patient can relapse.
“Most often, the site of the metastasized cancer is in the bone.”
“Now we know how they are getting in."
“We also identified an important mechanism that allows them to remain anchored in the bone marrow."
“In the mouse, our findings could offer new strategies to intervene at the molecular level before dormant cells can take hold and cause relapse.”
The E-selectin inhibitor used in the mice study, called GMI-1271, is already being used in separate human clinical trials.
Professor Sipkins said she hoped to conduct additional studies in mice to better understand how breast cancer cells migrate through the body before moving on to human studies.
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