Strategy Sensitizes Tumors while Protecting Normal Tissues in Mice from Radiation Damage

Researchers at NCI and other institutes have developed a method that protects healthy tissues from the damaging effects of radiation treatment, while at the same time delaying tumor growth. Radiation is part of the treatment plan for over half of all cancers, but the risk of damage to healthy tissues limits the dose that can be delivered to tumors. The research team's findings may eventually allow for more aggressive radiation therapies for the treatment of cancer and lead to enhanced treatment responses.

Radiation damages DNA and some large molecules in cells and elicits stress responses that lead to cell death. Thrombospondin-1, a protein that is produced by a variety of cell types, has been shown to limit cell recovery from several types of stress via signaling through its receptor, CD47. Previous research has demonstrated that mice lacking thrombospondin-1 or CD47 are resistant to radiation damage. In the new study, the researchers showed that blocking the interactions of thrombospondin-1 and CD47 conferred protection from radiation damage to human cells and to normal tissues in mice. The team injected an agent that targets CD47 into one hind leg of mice that then received radiation therapy directed to the treated leg. They found that temporary suppression of CD47 expression protected the skin, muscle, and bone marrow from damage by radiation. The team next administered the CD47-targeting agent to tumor-bearing mice and followed tumor growth rates after radiation therapy. Blocking CD47 expression increased the sensitivity of tumor cells to radiation. The researchers observed that mice with melanoma tumors and lung tumors had 89 percent and 71 percent smaller tumors respectively compared to mice that did not receive the agent prior to radiation therapy. The study appeared online October 21, 2009, in Science Translational Medicine.

source: National Cancer Institute press release