Study Shows How Radiation May Alter the Microenvironment of Tissue Cells Leading to the Development of Breast Cancer

A study by researchers at the NYU Cancer Institute, an NCI-designated cancer center, suggests radiation raises the risk of cancer by altering the microenvironment of tissue cells and the communication between cells. In addition, the study found an aggressive type of breast cancer appears to be especially linked to radiation exposure. The study was published in the journal Cancer Cell.

“Our research shows that radiation has long-lasting effects on the microenvironment of tissue cells that contributes to the risk of developing cancer,” said Mary Helen Barcellos-Hoff, PhD, director of Radiation Biology and professor in the Department of Radiation Oncology at NYU Langone Medical Center.  “Although radiation therapy for cancer is extremely effective, it comes at a price of an increased cancer risk. These findings may help develop new ways to reduce the risk of radiation cancers.”

High doses of radiation are known to cause cancer in humans, which is usually attributed to its ability to damage DNA. However, this study suggests that in addition to damaging DNA, radiation may play a larger role in carcinogenesis by altering the way in which cells communicate with each other.

Breast cancer usually arises in the epithelial cells that line the mammary glands. NYU Cancer Institute researchers tested radiation’s carcinogenic potential on the microenvironment of tissue cells using a mammary chimera mouse model. This mouse model combined an irradiated animal and newly transplanted healthy, non-cancerous epithelial cells. In the study, all mice had the epithelial cells from their mammary glands surgically removed. Some received a dose of radiation comparable to several CT scans, and were subsequently transplanted with healthy epithelium genetically primed to develop cancer. Another group were not irradiated after the initial surgery, but received the primed epithelium. Still others were irradiated but transplanted with normal epithelium. 

Compared to the other groups of mice, those who were irradiated and received the primed transplants most rapidly developed an aggressive breast cancer that had the same features as human breast cancer in women who had received radiation therapy in their youth. Moreover, the cancers in these mice, like in humans, were estrogen receptor-negative. Other types of cancers developed in the other groups of mice, but were not as aggressive.  In addition, subsequent experiments determined that certain proteins and genes were especially associated with accelerated tumor growth. 

The study raises the possibility that cancer risk after radiation exposure can be decreased by inhibiting the alteration of tissue cells and proteins that promote tumor growth. The study suggests future therapies may target these cellular changes that occur in the microenvironment of tissue cells.

This study was done in  collaboration with Lawrence Berkeley National Laboratory; The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research; University of California, Davis, CA; Pioneer Valley Life Sciences Institute, Springfield, MA; University of Massachusetts; Michigan State University; Baylor College of Medicine and Korea University, Seoul, Korea.

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Thursday, June 30, 2011