A protein that triggers the growth of blood vessels appears to play a key role in the development of Kaposi's sarcoma. The finding, reported in tomorrow's issue of the Proceedings of the National Academy of Sciences, may lead to better treatments for the disfiguring and potentially deadly cancer that strikes nearly one-third of AIDS patients.
Pathologist Parkash Gill and his colleagues at the University of Southern California's School of Medicine had suspected that vascular endothelial growth factor (VEGF), a protein that regulates blood vessels' permeability as well as spurring their growth, might be involved in Kaposi's sarcoma because the tumors--which appear as purple blotches on the skin--have twisted masses of disorganized blood vessels and leaky capillaries. The team found that Kaposi's sarcoma cells did indeed produce scads of VEGF. They also noted that tumor cells had high levels of two protein receptors that bind to VEGF, while skin cells from adjacent, unaffected areas had no receptors.
Gill's group next tried to block VEGF with the hope of preventing tumor growth. They injected antisense DNA--a sort of mirror image of the stretch of DNA in the gene coding for the VEGF protein--into mice with the tumors. The antisense DNA can bind to a cell's RNA template for the protein, thus strangling its production. The treatment seemed to work: Tumors in mice that received the antisense DNA did not grow as quickly as those in mice that received random DNA fragments.
"If it holds up that VEGF is a very central player" in Kaposi's sarcoma, says Harvard University cell biologist Judah Folkman, it may open several treatment avenues. Although the initial antisense DNA tests were promising, Gill says compounds that block the VEGF receptors may also prove out as a weapon against the cancer, which can kill patients when tumors invade the lungs or other organs.