Conditions

Mystery Of How Breast Cancer Spreads Now Solved: Two Different Stem Cell States Required For Metastasis

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Breast cancer spreads because of two stem cell states, one that travels to distant parts of the body and another that replicates the tumor once it gets there. Alexis Fam Photography, CC BY 2.0

Scientists have discovered the channels through which breast cancer cells proliferate in the body, according to a new study led by a group of international researchers. The cancer’s stem cells exist in two states, and each was found to play a distinct role in mediating the process of metastasis — the spread of cancer from its epicenter to surrounding body parts.

Researchers have known for some time that metastasis is what makes cancer truly lethal. It’s the difference between “catching it early” and it “being too late.” Some cancers, like brain cancer and ovarian cancer, metastasize quickly, making treatment extremely difficult for oncologists to remove each part of the tumor. Others, such as prostate cancer, tend to spread slowly, remaining mostly localized. In both cases, the true threat lies in the spread, not the tumor themselves. A centralized tumor in a woman’s breast only starts to pose a grave threat once it begins to spread. It’s this transition, the present researchers argue, that is critical to sapping breast cancer of its lethality.

“We have evidence that cancer stem cells are responsible for metastasis — they are the seeds that mediate cancer’s spread,” said senior study author Dr. Max Wicha, director of the University of Michigan Comprehensive Cancer Center, in a recent statement. “Now we’ve discovered how the stem cells do this.”

The two basic states work in tandem. First there is the EMT state (epithelial-mesenchymal transition state). Located on the outer layer of the tumor, the stem cells appear dormant, despite being able to penetrate into the bloodstream and travel to distant parts of the body. Once there, the stem cells transition into the opposite state, dubbed the MET state (mesenchymal-epithelial transition state). That’s when the damage starts. The stem cells replicate and grow, producing new tumors to repeat the destructive process. If either state can’t perform its function, Wicha says, then the spread stops.

“You need both forms of cancer stem cells to metastasize and grow in distant organs,” he explained. “If the stem cell is locked in one or the other state, it can’t form a metastasis.” Think of it like a game of telephone, where each step in the process depends upon the previous one to work smoothly. If a single glitch disrupts the stem cell’s function, the entire spread fails.

Harder than discovering this basic two-step understanding, unfortunately, will be finding the regulatory pathways that keep these stem cells working like clockwork. For cancer therapies to be effective, doctors need to know which processes perform which functions so they can target multiple pathways at once. Sadly, the current tests that track a tumor’s journey through a patient’s bloodstream don’t screen for EMT stem cells. Wicha and his colleagues are working alongside the University’s engineering researchers to develop tools that can fill this need.

It’s a need that deserves urgent attention, too. Breast cancer is the most common cancer in women, killing just over 41,000 people in the U.S. in 2010, according to the Centers for Disease Control and Prevention. More than 200,000 women were diagnosed with breast cancer in that same year. Wicha says the research should open new doors for developing treatment options.

“Now that we know we are looking at two different states of cancer stem cells,” he concluded, “we can use markers that distinguish these states to get a better sense of where the cancer stem cells are and to determine the effectiveness of our treatments.”

 

 

Source: Liu S, Cong Y, Wang D, et al. Breast Cancer Stem Cells Transition between Epithelial and Mesenchymal States Reflective of their Normal Counterparts. Stem Cell Reports. 2014.

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