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Human iPS cells offer a convenient means to study cancer growth. Injected into mice with compromised immune systems, they generate chaotic but benign tumors composed of many kinds of tissue. When the researchers injected iPS cells derived from a chromosomally normal individual, the resulting tumors spawned elaborate networks of blood vessels to feed themselves. But when Ryeom’s team injected iPS cells derived from a Down syndrome patient, the tumors formed hardly any blood vessels at all.

In addition, the stem cell approach could allow the researchers to zero in on other potential anti-angiogenic proteins on chromosome 21 by tweaking gene copy numbers in the iPS cells. “We basically can map which genes are necessary in human Down syndrome cells to block blood-vessel growth,” says Ryeom. The iPS cells could also be used to test potential DSCR1-like drugs.

“The idea of being able to combine a mouse model of disease with actual human cells in culture is very attractive,” says Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute in La Jolla, CA, who was not involved in the research. “It’s a really big step forward.”

Now that Ryeom and her colleagues have shown the importance of the DSCR1 pathway in blocking tumors, the researchers are testing it as a potential target for cancer drugs. By chopping the protein into tiny pieces, they have identified the smallest chunk required to interfere with abnormal blood-vessel growth. Ryeom envisions using that chunk not just as a treatment for cancer, but also perhaps as a prophylactic.”If we could take this as sort of a preventative, vitamin-like therapy,” she speculates, “would it block all of us from having tumor cells grow into these huge, lethal masses?”

Debabrata Mukhopadhyay, a professor of biochemistry and molecular biology at the Mayo Clinic Cancer Center in Rochester, MN, advises caution. He says that because the role of DSCR1 in normal development isn’t yet well understood, toying with its biological pathway might have unintended consequences. He is optimistic, though, that the new study will help researchers begin to decipher that mechanism.

“If there is any distinct difference between DSCR1’s effect on pathological versus physiological angiogenesis, that needs to be resolved,” says Mukhopadhyay. “But this is a very important way of looking for anti-angiogenic therapy.”

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Credit: Kwan-Hyuck Baek et al., Children’s Hospital Boston

Tagged: Biomedicine, cancer, stem cells, iPS cells, Down Syndrome, tumors

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