Stress Spreads Breast Cancer to Bone

(Ivanhoe Newswire) – Investigators from the Vanderbilt Center for Bone Biology have discovered that stress can promote the colonization of breast cancer cells in bone.

Mice studies revealed that the activation of the sympathetic nervous system (the "fight or flight" response) primes the bone environment for breast cancer cell metastasis. Researchers were able to prevent breast cancer cell lesions in bone using propranolol, a cardiovascular medicine that inhibits sympathetic nervous system signals.

Metastasis is the spread of cancer cells to distant organs, including bone; it is more likely to kill patients than a primary breast tumor.

Florent Elefteriou, Ph.D., director of the Vanderbilt Center for Bone Biology, was quoted as saying, "Preventing metastasis is really the goal we want to achieve."

Elefteriou and colleagues knew that the sympathetic nervous system stimulated bone remodeling, and it used some of the same signaling molecules that have been implicated in breast cancer metastasis to bone.

"We came to the hypothesis that sympathetic activation might remodel the bone environment and make it more favorable for cancer cells to metastasize there," Elefteriou was quoted as saying.

Clinical evidence supported this hypothesis. Breast cancer patients who suffered from stress or depression following primary treatment had shorter survival times. Both stress and depression trigger the sympathetic nervous system.

To investigate this link, researchers looked at cancer cell metastasis in mice. They followed fluorescently "tagged" human breast cancer cells that were injected into the mouse heart to simulate the stage of metastasis when breast cancer cells leave the primary site and move through the circulation.

Treating the mice with a drug that imitates sympathetic nervous system activation caused more cancer lesions in bone. Stressing the mice with physical restraint activated the sympathetic nervous system and caused more cancer lesions in bone. Treating the restrained mice with propranolol, one of a family of blood pressure medicines called "beta-blockers," reduced the amount of bone lesions.

Sympathetic nervous system activation increases bone levels of a signaling molecule called RANKL, which is known to promote the formation of osteoclasts (bone cells that break down bone tissue). RANKL has also been associated with cell migration; Elefteriou and colleagues showed that breast cancer cell migration to the bone depends on RANKL.

The study’s findings suggest that beta-blockers or drugs that interfere with RANKL signaling, like denosumab, could useful in preventing breast cancer cell metastasis to bone. Propranolol and other beta-blockers are inexpensive, well-characterized, and safe in most patients. They may also be a good choice for long-term treatment if future studies in breast cancer patients confirm their ability to block cancer cell metastasis to bone.

"If something as simple as a beta blocker could prevent cancer metastasis to bone, this would impact the treatment of millions of patients worldwide," Elefteriou was quoted as saying.

Meanwhile, efforts to reduce stress and depression in cancer patients may have unappreciated benefits in preventing metastasis.

Source: PLoS Biology, July 2012

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