Genetic Switch Found For Growth Of Common Childhood Tumor
Researchers have discovered a mechanism for the rapid growth seen in infantile hemangioma, the most common childhood tumor.
Made up of proliferating blood vessels, hemangiomas affect up to 10 percent of children of European descent, with girls more frequently afflicted than boys. The growths appear within days of birth—most often as a single blood-red lump on the head or face—then grow rapidly in the ensuing months. The development of infantile hemangioma slows later in childhood, and most tumors disappear entirely by the end of puberty.
Though the tumors are benign, they can cause disfigurement and clinical complications. The study offers hope for the most severe of these cases, pointing to a potential, noninvasive treatment.
The findings, from a collaboration of scientists at HSDM, HMS, Children's Hospital Boston, and the de Duve Institute at the Catholique University of Louvain in Brussels, appeared online Oct. 19 in Nature Medicine.
The researchers looked at tissue isolated from nine distinct hemangioma tumors, finding that the endothelial cells that lined the affected blood vessels were all derived from the same abnormal cell. Like other tumors, hemangiomas are caused by the abnormal proliferation of tissue. Since no other type of cell within the tissue displayed the same self-replicating tendency, the scientists concluded that the endothelial cells were the source of the tumors' growth.
Looking further, the team discovered that these cells behaved as if they were activated by a hormone called vascular endothelial growth factor (VEGF). The hormone usually binds to a specific receptor that prevents VEGF from signaling the cell to proliferate. The researchers found that at least two gene mutations were capable of setting off a chain of events that ultimately stymied these receptors, enabling VEGF to trigger unchecked growth in the endothelial cells.
The findings open up new treatment options, according to study leader Bjorn Olsen, dean for research and professor of developmental biology at HSDM and the Hersey professor of cell biology at HMS. First author Masatoshi Jinnin is a research fellow in developmental biology at the Dental School.
"What the data suggest," Olsen said, "is that any therapy that is directed against vascular endothelial growth factor—anti-VEGF therapy—is the rational therapy to use in these tumors."
Anti-VEGF therapies have already been approved for other conditions, including certain types of cancer. The next step for Olsen's team is to get approval to test the therapies in clinical trials.