Melanoma-initiating cell identified

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London, July 1 (ANI): A team of researchers at the Stanford University School of Medicine has discovered a cancer-initiating cell in human melanomas.

The finding is significant because the existence of such a cell in the aggressive skin cancer has been a source of debate.

It may also explain why current immunotherapies are largely unsuccessful in preventing disease recurrence in human patients.

"These cells lack the traditional melanoma cell surface markers targeted by these treatments. Without wiping out the cells at the root of the cancer, the treatment will fail," said post-doctoral fellow Alexander Boiko, the first author of the research.

To conduct the study, Boiko analyzed cell surface markers on primary melanoma tumor samples taken directly from patients at the Stanford Cancer Center.

In this way, he avoided having to grow the cells for a long period of time in the lab. Continuous culturing, or passage, of cancer cells often gives the cells time to evolve and change in ways that might not accurately reflect their composition in melanoma patients.

He found that one protein, called CD271, was always expressed on only a fraction of the cells in the human melanoma samples tested: The proportion of cells expressing CD271 varied in the samples from 2.5 to 41 percent of the total cell population; the marker appeared on a mean of 16.7 percent of cells in the samples.

This was interesting because CD271 was previously identified as a marker that identifies a group of cells called the neural crest stem cells. These cells are unique in that they are a multipotent, migratory cell population that becomes many cell types during development including melanocytes (cells responsible for skin pigmentation), bone, smooth muscle, neurons, and cartilage in the head and face.

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 further tested the tumor initiating properties of the cells expressing CD271. The researchers 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. Our research indicates that it may be more appropriate to also target cells expressing CD271," said Boiko.

Such a combination therapy might work to kill both types of cells in the tumor and, hopefully, prevent disease recurrence.

The study has been published in the July 1 issue of Nature. (ANI)

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