Certain Breast Cancer Cells Spur Metastasis to Bones

Researchers are coming a little bit closer to determining which breast cancer cells will go on to spread through the body, and which won't, but now a new study has found that certain cancer cells have a way of thriving that helps them move on to other parts of the body, like our bones.

According to newswise.com, "When a cancer cell sloughs off the edge of a tumor in the breast, it faces a tough road to survive. The cell must not only remain physically intact as it rushes through blood vessels, but it also must find a new organ to lodge itself in, take in enough nutrients and oxygen to stay alive, and begin dividing, all while escaping notice by the body’s immune system."

Scientists in the new study found that some loose breast cancer cells "have a leg up on survival—the genes they express make them more likely to prosper in bone tissue." Newswise.com reports that the team also found that whether or not cancer cells turn on those genes depends on what their surroundings were like in the primary breast tumor. "If the breast tumor had molecular patterns similar to those found in bone, the tumor is more likely to spread to bone later," the site notes.

“It’s like in society -- who you hang out with shapes who you are,” newswise.com quotes study investigator Joan Massagué of Memorial Sloan-Kettering Cancer Center. “And that might make you better or worse equipped to handle situations you’ll encounter.”

Although it sounds pretty depressing if you have, or had, breast cancer, the findings may result in new drugs that block cancers from spreading to bone or other organs, according to Massague.

"When cells from a primary tumor circulate through the body and begin growing in a new organ, a metastatic tumor is formed," newswise.com explains. "Such metastases are often harder to treat than primary tumors; the vast majority of people who die of cancer have not only a primary tumor but also metastatic disease."

That makes it a major goal of cancer researchers to not only find ways to treat primary tumors, but stop cancer from metastasizing.  We're not there yet, but we're getting closer.

Massagué’s lab group discovered in 2009 that by looking at the genetics of breast cancer cells, they could predict which were most likely to spread to bone. But the researchers didn’t know why. “What was really a conundrum was how this pathway got turned on in the first place,” newswise.com quotes Massagué, "because these genes didn’t confer any survival benefit to cells in the primary tumor. We were really at a loss for clues.”

So the tested whether there were any other genes, outside the known pathway, that were always turned up on down in the same cells. They found two other genes that were not only found to be "more highly expressed in tumors with (the original genes), but were also independently predictive of which tumors would migrate to the bone. Tumors with both genes turned up were more likely to lead to bone metastases."

Tumors consist of not only cancerous cells, but also other supporting cells that are integrated into the tumors’ structure. "The gene signature, it turned out, was coming from noncancerous mesenchymal cells integrating into the breast tumor," newswise.com says.

“This was the eureka moment,” says Massagué. “We realized there was mimicry between the environment of a primary tumor, and the environment of their preferred organ of metastasis.”

Not to get too technical about it, but the newly discovered gene signature, while it doesn’t significantly change primary breast tumor growth, "makes cancerous cells slightly more sensitive to the cytokines (signaling molecules) produced by the mesenchymal cells. Then, because they are more sensitive to these cytokines, if the cells end up in bone tissue that expresses higher levels of the same cytokines, they will grow more aggressively, Massague notes.

“For any cancer cell, it’s dreadfully rough to survive in the body after leaving a tumor,” Massagué tells newswise.com. “These cells selected for being more responsive to cytokines might just have this tiny extra chance of surviving in bone, but when you’re talking about tens of thousands of cancer cells circulating in the body per day, that tiny extra chance is enough to change the odds of a metastatic tumor forming.”

Researchers believe that the environment of a primary tumor can give cancer cells varied abilities to lodge in other organs — and likely applies to other cancer types and metastasis sites as well.  The team is working on ways to prevent this from happening.






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