Brain tumor treatment may increase number of cancer stem-like cells

Mar 05, 2009

A new study suggests that the standard treatment for a common brain tumor increases the aggressiveness of surviving cancer cells, possibly leaving patients more vulnerable to tumor recurrence. The research, published by Cell Press in the March 6th issue of the journal Cell Stem Cell, provides valuable insight into the molecular mechanisms that enable cancer stem-like cells to escape cytotoxic treatment and repopulate the tumor.

Glioblastoma multiforme is the most prevalent and aggressive form of primary brain tumor and is notoriously resistant to standard therapies. Dr. Eric Holland, from Memorial Sloan-Kettering Cancer Center in New York, examined the role of ABCG2, a protein linked with drug resistance, in glioma cancer stem-like cells. "ABC proteins are transporters that participate in tumor resistance by actively transporting drugs across the cell membrane, serving to protect cells from chemotherapeutic agents," offers Dr. Holland.

Dr. Holland and colleagues employed a method that allowed visualization of ABC-mediated efflux of fluorescent dye to identify and isolate "side population" (SP) cells from mouse and human glioblastomas. "Because the SP phenotype in glioma cancer stem-like cells is mainly mediated by ABCG2, as shown by the almost complete abolition of this phenotype when ABCG2 activity is blocked, we subsequently studied the oncogenic potential of ABCG2," explains Dr. Holland.

The researchers confirmed that SP cells are highly tumorigenic, have the ability to self-renew, and are resistant to chemotherapy. These results verified that ABCG2 activity, although not by itself oncogenic, is a marker for glioma stem-like cells. Further, the researchers identified a detailed molecular mechanism that modulates the activity of ABCG2 and enhances the ability of cancer stem-like cells to expel drugs.

Importantly, Dr. Holland's group also found that the chemotherapeutic drug temozolomide, the standard treatment for gliomas, increased the number of glioma cells with stem-like characteristics. The researchers speculated that because temozolomide is not an ABCG2 substrate, the increase in the SP fraction likely resulted from enrichment of cells with stem-like properties. "In the process of increasing the number of cells in tumors with stem-like properties, temozolomide may render surviving cells even more resistant to subsequent treatment with drugs that are substrates for ABCG2," explains Dr. Holland.

Source: Cell Press

Explore further: Six percent of colorectal cancer found to be interval tumors

add to favorites email to friend print save as pdf

Related Stories

Non-invasive technique to "light up" animal cells

Mar 21, 2014

A Florida State University scientist is part of a team of researchers that has developed a non-invasive way to "light up" animal cells, a development that could significantly advance cell-based therapies and pave the way ...

A key facilitator of mRNA editing uncovered

Feb 06, 2014

Molecular biologists from Indiana University are part of a team that has identified a protein that regulates the information present in a large number of messenger ribonucleic acid molecules that are important ...

Brain-penetrating particle attacks deadly tumors

Jul 02, 2013

(Phys.org) —Scientists have developed a new approach for treating a deadly brain cancer that strikes 15,000 in the United States annually and for which there is no effective long-term therapy. The researchers, ...

Recommended for you

Physicians target the genes of lung, colon cancers

11 hours ago

(Medical Xpress)—University of Florida physicians and researchers are collaborating to map the genes of different types of cancer, and then deliver medication to attack cancer at its source.

User comments : 0

More news stories

Down's chromosome cause genome-wide disruption

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

How kids' brain structures grow as memory develops

Our ability to store memories improves during childhood, associated with structural changes in the hippocampus and its connections with prefrontal and parietal cortices. New research from UC Davis is exploring ...

Ebola virus in Africa outbreak is a new strain

The Ebola virus that has killed scores of people in Guinea this year is a new strain—evidence that the disease did not spread there from outbreaks in some other African nations, scientists report.