How breast cancer usurps the powers of mammary stem cells

August 11, 2014
How breast cancer usurps the powers of mammary stem cells
Mammary cells found during pregnancy that express integrin beta3 (CD61) act as stem cells, capable of reconstituting a new mammary gland in mice. This property may be to blame for the more aggressive nature of beta3-expressing breast cancer cells. Shown is a section from a mammary 'outgrowth' harvested at lactation and immuno-stained for the epithelial markers E-cadherin (brown) and alpha-SMA (red). Credit: UC San Diego School of Medicine

During pregnancy, certain hormones trigger specialized mammary stem cells to create milk-producing cells essential to lactation. Scientists at the University of California, San Diego School of Medicine and Moores Cancer Center have found that mammary stem cells associated with the pregnant mammary gland are related to stem cells found in breast cancer.

Writing in the August 11, 2014 issue of Developmental Cell, David A. Cheresh, PhD, Distinguished Professor of Pathology and vice-chair for research and development, Jay Desgrosellier, PhD, assistant professor of pathology and colleagues specifically identified a key molecular pathway associated with aggressive breast cancers that is also required for mammary stem cells to promote lactation development during .

"By understanding a fundamental mechanism of mammary gland development during pregnancy, we have gained a rare insight into how aggressive breast cancer might be treated," said Cheresh. "This pathway can be exploited. Certain drugs are known to disrupt this pathway and may interfere with the process of breast cancer progression."

During pregnancy, a new mammary stem cell population arises, distinct from those involved in development and maintenance of the non-pregnant gland. These stem cells remodel the breasts and lactating glands in preparation for feeding the newborn child. Normally, these contribute only to early remodeling events and are switched off by the time milk production begins.

The researchers found, however, that signals regulating stem cell activation during pregnancy appear to be hijacked by to produce faster-growing, more aggressive tumors. "This normal pathway ends up contributing to the progression of cancer," said Desgrosellier, first author of the study.

A connection between pregnancy and breast cancer has long been known. But the association between pregnancy and is complex. While having a child reduces a woman's risk of developing breast cancer later in life, there is also an increased short-term risk for the development of a highly aggressive form of breast cancer following each pregnancy. The current study suggests that molecules important for stem cell behavior during pregnancy may contribute to these more aggressive pregnancy-associated breast cancers, a possibility the researchers plan to investigate further.

The authors are quick to point out that their findings should not be interpreted as a reason to avoid pregnancy. The signaling pathway usurped by cancer cells is not the cause of breast cancer. Rather, they said, it may worsen or accelerate a cancer caused by other factors, such as an underlying mutation or genetic predisposition.

"Our work doesn't speak to the actual cause of cancer. Rather, it explains what can happen once cancer has been initiated," said Cheresh. "Here's an analogy: To get cancer, you first have to start with an oncogene, a gene that carries a mutation and has the potential to initiate cancer. Think of the oncogene as turning on a car's ignition. The signaling pathway exploited by cancer cells is like applying gas. It gets the car moving, but it means nothing if the oncogene hasn't first started the process."

The researchers focused on a family of cell surface receptor proteins called integrins that act as key communications conduits, ultimately zeroing in on the role of one member of this family called beta-3 integrin. Also known as CD61, it was already linked to metastasis and resistance to cancer drugs.

Cheresh noted that CD61 represents a good marker for the incriminated signaling pathway involved in both mammary development during pregnancy and cancer. It's easily detected and could be used to both diagnose and treat breast cancer cases. "Detecting CD61 might help doctors determine what kind of therapeutic approach to use, knowing that they might be dealing with a more aggressive yet treatable form of . For example, there are existing drugs that block CD61 signaling, which might be another potential aspect of treatment."

Explore further: Breastmilk research may lead to medical breakthrough

Related Stories

Breastmilk research may lead to medical breakthrough

March 25, 2014
A researcher at The University of Western Australia has been awarded two major international grants to carry out further investigations into human breast milk.

Cancer stem cells linked to drug resistance

April 20, 2014
Most drugs used to treat lung, breast and pancreatic cancers also promote drug-resistance and ultimately spur tumor growth. Researchers at the University of California, San Diego School of Medicine have discovered a molecule, ...

Signalling protein plays different roles in breast cancer and normal cells

June 20, 2014
A key step in developing effective cancer therapies is identifying differences between normal, healthy cells and cancer cells – these differences can then be exploited to specifically kill tumour cells.

Research team identifies mechanism of chemotherapy resistance in inflammatory breast cancer

July 8, 2014
Researchers at Roswell Park Cancer Institute (RPCI) have identified a mechanism of breast cancer cells that leads to chemotherapy resistance in inflammatory breast cancer. These preclinical findings, published online ahead ...

A transcription factor called SLUG helps determines type of breast cancer

May 2, 2014
During breast-tissue development, a transcription factor called SLUG plays a role in regulating stem cell function and determines whether breast cells will mature into luminal or basal cells.

Cancer hijack

July 19, 2013
Genetically unstable breast cancer cells appear to hijack a mechanism used by healthy stem cells to determine how they should develop into different tissues, according to new research.

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.