The study provides the first genetic evidence that damage to the blood vessels that feed the tumor play a primary role in tumor regression. The blood vessel cells targeted by radiation are the endothelial cells, which are recruited by the tumor from the host to create the tumor microvasculature - a process called angiogenesis. Endothelial cells do not die in response to radiation due to DNA damage but rather by a specialized form of programmed cell death or apoptosis extensively studied at MSKCC. Understanding this form of radiation-induced cell death may ultimately have an effect on the treatment of cancer patients, approximately 50% of whom receive radiation therapy.
To study how endothelial cells within tumors respond to radiation, the researchers used a mouse model genetically engineered to be deficient in acid sphingomyelinase (asmase), an enzyme needed for endothelial cells to undergo apoptosis. When melanoma and fibro-sarcoma cells were implanted into mice, the tumors that developed in the acid sphingomyelinase deficient (asmase -/-) mice showed reduced endothelial apoptosis, had a tumor growth rate almost double that of the normal acid sphingomyelinase ( asmase +/+) mice, and were resistant to radiation-induced tumor regression.
"Our study confirmed that acid sphingomyelinase affects the endothelium
and that in turn plays a role in a tumor's growth and its response to
radiation," explained Monica Garcia-Barros, PhD, a member of Memorial
Sloan-Kettering's Signal Tran
Contact: Joanne Nicholas
Memorial Sloan-Kettering Cancer Center