When Boiko transplanted the melanoma cells from nine human samples into laboratory mice with severely compromised immune systems, he found that the cells expressing CD271 on their surface were much more likely to cause cancers in the recipients than those from the same tumor that didn't express the marker (70 percent versus 7 percent, respectively). And all but one of the newly induced tumors arising from the transplantation of the CD271-positive cells went on to develop a population of a mixture of CD271-expressing and non-expressing cells indicating that the cells with the marker were both self-renewing and differentiating into other types of tumor cells.
Boiko then collaborated with researchers in the medical school laboratories of professor of surgery Michael Longaker, MD, and assistant professor of surgery George Yang, MD, to further test the tumor initiating properties of the cells expressing CD271. They transplanted normal human skin on to the backs of the immunocompromised mice and injected the skin with the melanoma cells. Only cells expressing CD271 (isolated from melanomas from two patients) gave rise to tumors and lung metastasis in the mice.
Finally, the researchers looked to see whether the cancer-initiating cells also expressed common cellular antigens currently used for melanoma therapy. They found that melanoma cells expressing CD271 either completely or partially lacked expression of three common therapeutic targets TYR, MART and MAGE in 86 percent, 69 percent and 68 percent of melanoma patients, respectively.
"This could be the reason why we often see melanoma patients relapsing and coming back to the clinic," said Boiko. "Our
|Contact: Krista Conger|
Stanford University Medical Center