Growing breast cancer stem cells to get at the tumor’s root

By Heather Buschman, Ph.D.
October 3, 2012
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Today is Stem Cell Awareness Day, sponsored by the California Institute for Regenerative Medicine. Read about some new research on cancer stem cells below, and learn more about stem cells and clinical trials at an event tonight at the Sanford Consortium for Regenerative Medicine in La Jolla, Calif.

Not all cells that make up a tumor are necessarily the same. Recent research suggests that a special population of cancer stem cells might be at the root of some tumors. These stem cells can self-renew, generating both tumor cells and more stem cells. Cancer stem cells may be one reason that some tumors become resistant to standard therapies. They could also be the reason some tumors reappear—in actuality, the cancer stem cells never truly disappeared.

A Sanford-Burnham research team recently isolated cancer stem cells from a mouse model of breast cancer and showed that these cells are able to generate new tumors similar to the ones from which they originated—even when starting from just a single cell.

“Now that we can propagate this population of cancer stem cells, we can begin searching for new therapeutic compounds that inhibit or prevent the progression of some types of breast cancer,” said Robert Oshima, Ph.D., professor in Sanford-Burnham’s National Cancer Institute-designated Cancer Center and senior author of the study. These findings were published in the journal Stem Cells.

To get breast cancer stem cells, Oshima and his team, including postdoctoral researchers David Castro, Ph.D. and Jochen Maurer, Ph.D., searched for kinase inhibitors that might help them do the job. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth. After testing many, they found that inhibitors of one particular kinase—called ROCK1—dramatically stimulate growth of these breast cancer stem cells in a laboratory dish. The cancer stem cells self-renew, making more stem cells, but don’t easily specialize into other cell types when kept in a low-oxygen environment, as is found within tumors.

Human breast cancer stem cells that are similarly stimulated by ROCK1 inhibition and restricted oxygen will provide the opportunity to identify new therapeutic targets to prevent breast tumor recurrence.

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This research was funded by the Department of Defense (Breast Cancer Research Program grant BC093655) and the National Cancer Institute (Cancer Center Support Grant 5 P30 CA030199 and Postdoctoral Training Grant T32 CA121949).

Original publication:
David J. Castro, Jochen Maurer, Lionel Hebbard, & Robert G. Oshima (2012). ROCK1 Inhibition Promotes the Self-Renewal of a Novel Mouse Mammary Cancer Stem Cell Stem Cells DOI: 10.1002/stem.1224

ResearchBlogging.org

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Heather Buschman, Ph.D.

Heather was a Sanford-Burnham Communications staff member.

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