Mike Rogers (Garvan Institute)
6 November 2014. Medical researchers at the Garvan Institute in Sydney, Australia found common drugs to treat bone loss could treat breast and other other tumors outside the skeleton. The team led by Garvan research fellow Mike Rogers, with colleagues in Scotland and the U.S., published its findings online in the journal Cancer Discovery (paid subscription required).
Rogers and colleagues investigated a phenomenon reported in clinical trials where some women with breast cancer were given bisphosphonates, established widely-prescribed drugs to treat bone loss due to osteoporosis, and found less spread of their cancers and longer survival times. Bisphosphonates have a high affinity for calcium crystals in bone, where they bind with and deposit into the weakened bone structure. These drugs are also used to treat weakening of bone tissue in multiple myeloma and late-stage cancers that spread to bones.
The Garvan team looked into the way bisphosphonates work for clues to their effects on cancers unrelated to bones. They identified a possible link in tiny calcium deposits associated with breast tumors that sometimes appear in mammograms, and conducted tests with bisphosphonates for a connection between the drugs and breast tumors.
In tests on lab mice with mammary tumors and treated with bisphosphonates, researchers found aberrant immune system cells called macrophages that would normally attack healthy tissue instead attacked the tumor cells with calcium deposits. Bisphosphonates, the team discovered, bind to the minute specks of calcium in much the same way they bind to the calcium in bone. The macrophages then attack tumor cells with bisphosphonates attached instead of healthy tissue.
“We do not yet fully understand how the macrophages revert from being ‘bad cops’ to being ‘good cops’,” says Rogers in a Garvan Institute statement, “although it is clear that this immune cell interacts with tumors, and probably changes its function in the presence of bisphosphonates.”
The researchers were able to witness and record this process occurring in real time, using a form of laser scanning microscope. The team treated the bisphosphonates with a fluorescent stain and watched as the macrophages surround and devour the tumor cells. “I clearly remember the moment we first saw macrophages behaving like little Pacmen and gobbling up the drug,” says co-author Tri Phan. “It was astounding.” (See video below)
The team then repeated the test with human tumor tissue from a breast cancer patient in an affiliated hospital, and found the same actions occurring of macrophages attacking bisphosphonate-bound cells as they witnessed in mice. The researchers next plan to analyze the changes happening in macrophages to better understand the process that changes their actions from attacking healthy tissue to attacking cancer cells.
The following brief (12-second) video shows a macrophage, in green, absorbing a red-stained complex of calcium and bisphosphonates in a breast tumor.
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