Scientists from Johns Hopkins and from the University
of Milan have effectively proven that they can inhibit
lethal human brain cancers in mice using a protein that
selectively induces positive changes in the activity of
cells that behave like cancer stem cells. The report was
published last week in Nature.
The most common type of brain cancer —
glioblastoma — is marked by the presence of these
stem cell-like brain cells, which, instead of triggering
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 treatment experiment, the researchers 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
First they pretreated human glioblastoma cells with
bone morphogenic protein 4, or BMP4, then injected these
treated cells into mouse brains. In mice injected with
cells that were not pretreated, large, invasive cancers
grew. In the mice with BMP4-treated cells, no cancers grew
at all. Three to four months after injection, all mice that
got untreated cells died, and nearly 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 percent 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," said Alessandro Olivi, director of the
Division of Neurosurgical Oncology at Johns Hopkins and a
contributor to the study.
Olivi said that clinical studies using BMP4 could
begin within a year and, if they are successful, drug
therapies could be available to the public within three to
Henry Brem, chairman of the Department of
Neurosurgery at Johns Hopkins and a collaborator in the
study, said, "This was proof of the idea that BMPs could
stop glioblastoma by depleting the stem cell-like
population that feeds it. This opens exciting doors to
future research into treatments and therapies for such a