Researchers track the origins of breast cancer

Disease and treatment 28. dec 2017 3 min Associate Professor Lone Rønnov-Jessen Written by Morten Busch

Avoiding cancer requires preventing it before it develops. The challenge is to identify the cells in which cancer typically originates and to understand how it develops. Researchers have now succeeded in monitoring the development of breast cells outside the human body. This new technique provides hitherto unprecedented insight into the processes that can lead to breast cancer and the hope that it may help to diagnose and treat breast cancer in time.

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Normal cells that mutate into cancer cells often lose the ability to sense their microenvironment. The cells divide unimpeded, damage the surrounding tissue and spread to other parts of the body if left untreated. Since reversion of this behaviour is almost impossible, the cancerous tissue has to be destroyed or removed completely instead. This often has severe mental and physical consequences for breast cancer patients. Although researchers have suspected which cells in the female breast can become cancerous for decades, detailed investigation of their characteristics has not been possible.

“Because the development of cancer cannot be studied inside the breast, it is necessary to culture breast cells in a laboratory. It has, however, been extremely difficult to recapitulate the cellular development of the breast in culture. It is therefore a major breakthrough that we have now developed a system that enables us to culture specific types of stem cells from the breast. This will enable us to begin to study how normal cells develop and thereby also to unravel what happens when things go wrong,” explains the study’s senior author, Lone Rønnov-Jessen, Associate Professor, Department of Biology, University of Copenhagen.

Inner and outer parts of the breast differ

The human mammary gland comprises a branching duct system with an inner layer of luminal epithelial cells that can produce milk and an outer layer of myoepithelial cells that can contract upon suckling and eject the milk. The duct system that ends at the nipples leads down to deeper grape-like structures called terminal duct lobular units (TDLUs). About 3 of 4 breast cancer cases are believed to arise here. Although the stem cells that lead to breast cancer were already identified in 2003, further investigation has been challenged by the difficulty in culturing fully functional stem cells from the breast outside the human body.

According to Lone Rønnov-Jessen, “Stem cells generally give rise to other cells, which typically grow more rapidly than the stem cells. In addition, traditional culturing methods eliminate their stem cell properties. As a result, we have also had difficulty in monitoring their development. Now our new culturing methods enable us to do this.”

The researchers can therefore now begin to study whether the breast contains more than one type of stem cell. They can also elucidate how these cells develop under normal conditions and how the cells respond when exposed to chemicals and situations that can provoke cancer. The new study has been published in the Proceedings of the National Academy of Sciences of the United States of America, and this prominent placement underscores the importance of this new technique.

Our preliminary results show that the ducts and TDLUs comprise different types of stem cells. Those in the ducts are bipotent, meaning that they can differentiate in two directions, in contrast to the stem cells in the TDLUs, which are multipotent. We hope that, based on these differences, we can unravel why cancer most often develops in the TDLUs.

Fatal interaction

Currently, at least six subtypes of breast cancer are known but recognized only as the fully developed tumours. So far, very little is known about their origin and what triggers their development. The hope is that researchers can gain more insight into these aspects now that the individual cell types can be cultured outside the human body.

“We do not even know for sure whether the different types of cancer originate from the different cell types within the normal tissue or whether the different cancer types actually have the same origin. We hope that this new method will help to explain why the six different types of cancer progress so differently and why, for instance, women who have not breast-fed and whose breast glands have therefore not fully matured have a greater risk of developing breast cancer.”

Ultimately, the researchers aim to unravel hitherto unknown differences between healthy cells and cancer cells, which eventually can lead to novel treatments aimed at preventing the fatal interaction between the cancer cells and the surrounding connective tissue that causes the cancer to spread. The new technique is essential in this endeavour.

“If we can identify the properties healthy cells lose when they mutate into a cancer cell, we may become better at diagnosing the disease at an early time and possibly even re-establish normal cell behaviour and thus obstruct and eliminate the spread of cancer. More knowledge on which cells and cell mutations are responsible for cancer may help us to track the origins of breast cancer so that the cancer can be targeted very precisely,” concludes Lone Rønnov-Jessen.

Proof of region-specific multipotent progenitors in human breast epithelia” has been published in the Proceedings of the National Academy of Sciences of the United States of America. The article resulted from collaboration between the Department of Cellular and Molecular Medicine and the Department of Biology of the University of Copenhagen. Several authors are employed at the Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, University of Copenhagen.

With the aim of understanding development, homeostasis and carcinogenesis in human breast, we study cells from normal and cancerous breast with emphas...

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