Scientists studying cancer cells in humans commonly transplant them to grow human tumors in mice. It’s called a xenograft. Problem is the tumors don’t always grow in mice as they would in patients. But scientists at U-T Southwestern Medical Center have developed a xenograft model that consistently works in the study of skin cancer. Dr. Sean Morrison authored a study on this subject and talks about it in this week’s edition of KERA's Vital Signs.
We’ve developed a specialized way of doing a xenograft, in which the behavior of human melanomas – the deadliest form of skin cancer – is predictive of clinical outcome in the patients. That means that if the melanoma is going to spread and form aggressive disease in the patient, it will spread and form aggressive disease in the mice. And if it’s not going to spread in the patient and will be cured, it will also not spread effectively in the mice.
So you’ve developed a model that will give you an accurate prediction of how the cancer will spread in the human body?
That’s right. And the important thing about that is that it gives us the ability to study the molecular mechanism that regulates the ability of skin cancer cells to spread around the body. And once we understand those mechanisms we can develop new therapies to better treat the disease.
It is interesting that you’re just getting to this point. Skin cancer’s regarded as the most common form of cancer in the U.S., so I’m sure there’s been tons of research done before now, so has stood in the way of getting to this point?
On one hand, there’ve been a lot of advances in that we have a number of new therapies for melanoma that are effective in patients. The problem is that the therapies we have don’t cure very many patients, so there’s still a long way to go. And curing any kind of disease is a very complicated problem that requires a lot of research to understand the biological basis of the disease so we can try to intervene rationally to defeat it.
What was the point at which you actually realized this was going to work?
Well we noticed that when we took melanomas from patients and transplanted them into mice, we saw big differences in the way they behaved. Some of them spread very rapidly, some them didn’t spread at all. So we went back to the physicians that provided the melanomas and asked them to look at whether they saw any differences in the patients. And the first time we put up our lists side by side of the behavior of the tumor in the mice versus the behaviors of the tumor in the patients, we were shocked because the lists were almost identical. That’s when we first saw the correlation. On one hand, it was a breakthrough because no one had ever seen this before in a xenograft model. But on the other hand, it was a difficult moment because we realized the mice could tell us, before the physicians and patients would know, who was gonna die and who wasn’t gonna die and there was nothing we could do about it at that point.
What was it that led you to begin this?
My lab has historically has done a lot of work studying mechanisms that regulate stem cell function. And we studied the stem cells that give rise to melanocytes during development, and melanocytes are the cells that transform into melanoma. So we thought some of the techniques we developed to study the normal stem cells might be transferrable, and allow us to study melanoma in new ways and get new insights. And that’s turned out to be true.
So where will you go with this? What are the possibilities now ahead of us now that you’ve developed this model?
Well we didn’t like that feeling of knowing that we could predict what was gonna happen in the patients, but not having anything we could do about it. So, there’s new ideas coming out of our studies of these mice every day because the ability to study the biology in the mice profoundly expands what we’re able to do.
Dr. Sean Morrison is a stem cell expert who directs the Children’s Medical Center Research Institute at UT Southwestern.
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