Natural Protein Blocks Lethal Human Brain Tumors in Mice

Researchers have successfully demonstrated that they can suppress deadly human brain tumors in mice using a protein that selectively induces positive changes in the activity of cells that behave like cancer stem cells.

The most common type of brain cancer--glioblastoma--is characterized by the presence of stem-cell-like brain cells, which, instead of activating the replacement of damaged cells, form cancer tissue. Stem cells, unlike all other cells in the body, are capable of forming almost any kind of cell when the right signals trigger their development.

For their study, the researchers from Johns Hopkins University (Baltimore, MD, USA) and from the University of Milan (Italy) relied on a class of proteins, bone morphogenic proteins, that cause neural stem-cell-like clusters to lose their stem cell properties, which in turn stops their ability to divide.

The researchers first pretreated human glioblastoma cells with bone morphogenic protein 4 (BMP4), then injected these treated cells into mouse brains. In mice injected with cells that were not pretreated, large, invasive tumors grew. In the mice with BMP4-treated cells, no tumors grew at all. Three to four months after injection, all mice that got untreated cells died, and almost all mice with BMP4-treated cells were alive.

Next, the scientists delivered slow-release BMP4-containing "beads” directly into mouse brains with implanted glioblastoma cells. Mice that got empty beads developed large malignant tumors and died. Mice with BMP4 beads survived much longer, and 80% survived four months after cancer cell implants.

"Our idea is to treat patients with BMP4 or something like it right after surgery to remove glioblastoma in hopes of preventing the regrowth of the cancer and improving survival time,” stated Alessandro Olivi, M.D., director of the division of neurosurgical oncology at Johns Hopkins and an author of the study.

Dr. Olivi reported that clinical studies using BMP4 could begin within a year and, if effective, drug therapies could be available to the public within three to four years. "This was proof of the idea that BMPs could stop glioblastoma by depleting the stem-cell-like population that feeds it,” reported Henry Brem, M.D., chairman of the department of neurosurgery at Johns Hopkins and a collaborator in the study. "This opens exciting doors to future research into treatments and therapies for such a devastating disease.”

The findings were published in the December 7, 2006 issue of the journal Nature.



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