Study finds inflammation caused by radiation can drive triple-negative breast cancer

February 24, 2020

Wilmington, DE, February 24, 2020 -- While radiation is successfully used to treat breast cancer by killing cancer cells, inflammation caused as a side-effect of radiation can have a contrary effect by promoting the survival of triple-negative breast cancer cells, according to research published online in the International Journal of Radiation Biology by Jennifer Sims-Mourtada, Ph.D., director of Translational Breast Cancer Research at ChristianaCare's Helen F. Graham Cancer Center & Research Institute.

Accounting for 15-20% of all breast cancers, triple-negative breast cancer is faster growing than other types of breast cancers.

Dr. Sims-Mourtada's latest study, "Radiation induces an inflammatory response that results in STAT3-dependent changes in cellular plasticity and radioresistance of breast cancer stem-like cells," brings scientists closer to understanding the mechanisms behind this aggressive and hard-to-treat cancer. It shows that inflammation caused by radiation can trigger stem-cell-like characteristics in non-stem breast cancer cells.

"This is the good and the bad of radiation," Dr. Sims-Mourtada said. "We know radiation induced inflammation can help the immune system to kill tumor cells -- that's good -- but also it can protect cancer stem cells in some cases, and that's bad."

She added, "What's exciting about these findings is we're learning more and more that the environment the tumor is in - its microenvironment - is very important. Historically, research has focused on the genetic defects in the tumor cells. We're now also looking at the larger microenvironment and its contribution to cancer."

The term triple-negative breast cancer refers to the fact that the cancer cells don't have estrogen or progesterone receptors and also don't make too much of the protein called HER2. The cells test "negative" on all 3 tests. These cancers tend to be more common in women under age 40, who are African-American, Latina or who have a BRCA1 mutation.

"My work focuses on cancer stem cells and their origination," Dr. Sims-Mourtada said. "They exist in many cancers, but they're particularly elusive in triple-negative breast cancer. Their abnormal growth capacity and survival mechanisms make them resistant to radiation and chemotherapy and help drive tumor growth."

She and her team applied radiation to triple-negative breast cancer stem cells and to non-stem cells. In both cases, they found radiation induced an inflammatory response that activated the Il-6/Stat3 pathway, which plays a significant role in the growth and survival of cancer stem cells in triple-negative breast cancers. They also found that inhibiting STAT3 blocks the creation of cancer stem cells. Still unclear is the role IL-6/STAT3 plays in transforming a non-stem cell to a stem-cell.

For women living in Delaware, Dr. Sims-Mourtada's research is especially urgent: The rates of triple-negative breast cancer in the state are the highest nationwide.

"At ChristianaCare, we are advancing cancer research to help people in our community today, while we also advance the fight against cancer nationwide," said Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute. "Dr. Sims-Mourtada's research is a dramatic step toward better treatments for triple-negative breast cancer."

To advance her research on inflammation, last year Dr. Sims-Mourtada received a $659,538 grant from the Lisa Dean Moseley Foundation. The three-year grant will enable her and her team at the Cawley Center for Translational Cancer Research to continue investigating the role of cells immediately around a tumor in spurring the growth of triple-negative breast cancer and a possible therapy for this particularly difficult cancer.

"Our next step is to understand the inflammatory response and how we might inhibit it to keep new cancer stem cells from developing," Dr. Sims-Mourtada said.

Dr. Sims-Mourtada's research team previously identified an anti-inflammatory drug, currently used to treat rheumatoid arthritis, that has the potential to target and inhibit the growth of cancer stem cells and triple-negative breast cancer tumors. That research could set the stage for clinical investigation of the drug, alone or in combination with chemotherapy, to improve outcomes for patients with triple-negative breast cancer.
-end-
Download images of Dr. Sims-Mourtada in the lab and of triple negative breast cancer cells.

About the Helen F. Graham Cancer Center & Research Institute

The Helen F. Graham Cancer Center & Research Institute, a National Cancer Institute Community Oncology Research Program, is part of ChristianaCare, one of the country's most dynamic health systems, centered on improving health outcomes, making high-quality care more accessible and lowering health care costs. With more than 232,000 patient visits last year, the Graham Cancer Center is recognized as a national model for multidisciplinary cancer care and a top enroller in U.S. clinical research trials. In conjunction with its Gene Editing Institute, the Cawley Center for Translational Cancer Research, the Tissue Procurement Center, statewide High-Risk Family Cancer Registry and collaborations with world-renowned scientists at facilities such as The Wistar Institute in Philadelphia scientists are opening new avenues to more quickly translate cancer science into cancer medicine. For more information, visit christianacare.org/cancer.

ChristianaCare's Cawley Center for Translational Cancer Research

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.