Scientists at Oregon Health Sciences University have discovered why AIDS patients frequently develop a form of cancer called B-cell non-Hodgkin's lymphoma. The work appears in the November issue of the journal Nature Medicine and sheds light on how viruses initiate transformations in cells that can lead to cancer.
"It has been observed for years that AIDS patients frequently succumb to a cancer of the lymphatic system called B-cell lymphoma," says Ashlee V. Moses, Ph.D., lead author of the paper and research assistant professor in molecular microbiology and immunology at OHSU. "But it has been unclear why this happens. We now propose an explanation for why B-cells often become cancerous in AIDS patients."
B-cells are important players in the immune system and respond to infection. Moses and colleagues discovered that although B-cells themselves never actually harbor HIV, they are recruited to fight off the invading virus.
"B-cells are recruited by special cells lining the tiny capillaries of the body, called endothelial cells," explains Moses. "Endothelial cells normally play a critical role in signaling immune cells to leave the blood stream and enter the tissues to fight and destroy invading organisms. However in AIDS patients, the endothelial cells are themselves infected by HIV and their signaling mechanism goes awry."
Moses further explains that HIV infection of the endothelial cell causes an unusual cascade of molecular events culminating in cancerous transformation of the B-cell. The HIV- infected endothelial cell displays an abnormally large amount of a signaling molecule called CD40. This signal in turn induces an increased number of adhesion molecules to form on the surface of the endothelial cell. The adhesion molecules support the attachment and growth of malignant B-cells.
"If we could block HIV infection of the endothelial cell, we might be able to preclude the errant signaling that causes the B-cell to become cancerous," says Moses.