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Old theory helps discover new targets in fight against breast cancer

Washington, Wed, 08 Feb 2012 ANI

Washington, Feb 8 (ANI): In a new study, scientists have revived a theory first proposed in the late 1800s and studied organ development in mice to reveal how breast cancers, and possibly other cancers, develop in people.


According to the theory, the development of organs in the normal embryo and the development of cancers are related.


The findings by scientists at the Salk Institute for Biological Studies provide new ways to predict and personalize the diagnosis and treatment of cancer.


The scientists 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 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," said Geoffrey Wahl, a professor in Salk's Gene Expression Laboratory, who led the research.


"The system depends on internal instructions and external signals from the environment to tell the stem cell what to do and where to go in the body. 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."


The relationship between cancer and embryonic tissues was first proposed in the 1870s by Francesco Durante and Julius Cohnheim, who thought that cancers originated from cells in adults that persist in an immature, embryonic-like state.


More recently, scientists including Benjamin Spike, a co-first author on the current work and post-doctoral fellow in the Wahl lab, have discovered that tumours often contain cells with stem cell characteristics revealed by their genetic signatures.


As a result, many scientists and physicians are pursuing ways to destroy stem-like cells in cancer, since such cells may make cancer more resistant to treatment and may lead to cancer recurrence.


The Salk scientists are now characterizing the stem-like cells in certain forms of breast cancer to arrest their growth.


By focusing on tissue obtained from mouse embryos, the Salk researchers were able for the first time to identify and isolate a sufficiently large number of foetal breast stem cells to begin to understand how their GPS works.


The Salk scientists first made the surprising finding that these foetal breast stem cells were not fully functional until just prior to birth.


This observation suggested that a very special landscape is needed for a cell to become a stem cell. The breast stem cells at this late embryonic stage were sufficiently abundant to simplify their isolation.


This enabled their genetic signature to be determined, and then compared to that of the stem-like cells in breast cancers.


The signatures of the breast stem cells in the foetus were stunningly similar to the stem-like cells found in aggressive breast cancers, including a significant fraction of a virulent cancer subtype known as "triple-negative."


This is important as this type of breast cancer has until now lacked the molecular targets useful for designing personalized therapeutic strategies.


The study has been published in Cell Stem Cell. (ANI)



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