A New "Twist" in Breast Cancer

Date: November 11, 2010

Neoplasia, December 4, 2009
Working with mice, scientists have shown that a protein made by a gene called TWIST may be the proverbial red flag that can accurately distinguish cells that drive aggressive, metastatic breast cancer from other breast cancer cells.

Their findings build upon a growing body of work suggesting that a rare subgroup of cells, known as cancer stem cells, drive breast and other tumors. Scientists believe that this subgroup of cells has some very distinctive qualities and characteristics.

In experiments designed to identify those special qualities, the Hopkins team focused on the TWIST1 gene, a tumor-promoting gene named for the twisted shape of Drosophila (fly) embryos that lack TWIST.  It is what scientists refer to as oncogenic, one that if expressed when and where it’s not supposed to be, causes cancer because the molecules and pathways that once regulated it and kept it in check are gone.

“Our experiments show that TWIST is a driving force among a lot of other players in causing some forms of breast cancer,” says Venu Raman, Ph.D.  “The protein it makes is one of a growing collection of markers that, when present, flag a tumor cell as a breast cancer stem cell.”

Working with human breast cancer cells transplanted into mice, all of which had the oncogene TWIST, the scientists use fluorescent chemicals to track the cells. They counted 20 breast cancer stems cells and then injected them into the breast tissue of 12 mice. All of them developed cancerous tumors.

“Normally, it takes approximately a million cells to grow a xenograft, or transplanted tumor,” Raman says. “And here we’re talking just 20 cells. There is something about these cells – something different compared to the whole bulk of the tumor cell – that makes them potent. That’s the acid test – if you can take a very small number of purified “stem cells” and grow a cancerous tumor, this means you have a pure population.”

This finding – that TWIST is integral to the breast cancer stem cell phenotype – has fundamental implications for early detection, treatment and prevention, Raman says. Some cancer treatments may kill ordinary tumor cells while sparing the rare cancer stem cell population, sabotaging treatment efforts. More effective cancer therapies, he says, will likely require drugs that kill this important stem cell population.

This study was supported by the Maryland Stem Cell Research Foundation.