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Salk scientists use an old theory to discover new targets in the fight against breast cancer

Wahl Science

Mammary stem cells found in developing mouse embryos (pictured here against a background of fat tissue).

Image courtesy of Dannielle D. Engle

Reviving a theory first proposed in the late 1800s, a team of researchers led by Geoffrey Wahl reported striking similarities between genetic signatures found in certain types of human breast cancer and those of stem cells in breast tissue in mouse embryos. These findings, published in Cell Stem Cell, suggest that cancer cells subvert key genetic programs that guide immature cells to build organs during normal growth.

"Stem cells in a healthy developing embryo have a GPS system to alert them about their position in the organ," says Wahl. "It stimulates the stem cells to grow and form more stem cells or to change into different cells that form complex organs, such as the breast. Our findings tell us that this GPS system is broken during cancer development, and that may explain why we detect stem-like cells in breast cancers."

Studying the genetic activity of organ-specific stem cells is difficult because the cells are very rare, and it is hard to separate them from other cells in the organ. But by focusing on tissue obtained from mouse embryos, Wahl's group, which included Benjamin Spike, Dannielle Engle, Jennifer Lin, Justin La and Samantha Cheung, was able for the first time to identify and isolate a sufficiently large number of fetal breast stem cells to begin to understand how their GPS works.

The signatures of the breast stem cells in the fetus were stunningly similar to the stemlike cells found in aggressive breast cancers, including a significant fraction of a virulent cancer subtype known as "triple-negative," which until now lacked the molecular targets useful for designing personalized therapeutic strategies. The discovery of the shared genetic signatures provides a new avenue for scientists to explore the links between development and cancer. By uncovering new biological markers, Wahl and his team hope to develop tests that individualize treatment by showing how the GPS system of a tumor operates. This should help doctors determine which patients may benefit from treatment, and the correct types of treatment to administer.