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: Researchers reveal how pancreatic cancer cells sidestep chemotherapy

add to favorites email to friend print save as pdf

Related Stories

Team enlarges brain samples, making them easier to image

Jan 15, 2015

Beginning with the invention of the first microscope in the late 1500s, scientists have been trying to peer into preserved cells and tissues with ever-greater magnification. The latest generation of so-called ...

Research reveals structure of key CRISPR complex

Dec 10, 2014

Using a gene-editing system originally developed to delete specific genes, MIT researchers have now shown that they can reliably turn on any gene of their choosing in living cells.

New method solves centuries-old animal mystery

Dec 10, 2014

Most animal embryos contain three layers of cells that transform into every part of the body—from brains to bones to guts. Since the 19th century, biologists have been puzzling over which of these layers came first in animal ...

Recommended for you

Colon cancer rates rising among Americans under 50

Jan 30, 2015

(HealthDay)—Although the overall rate of colon cancer has fallen in recent decades, new research suggests that over the last 20 years the disease has been increasing among young and early middle-aged American ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.