The biology of intestinal stem cells and the genes that control it may be the key to understanding the origin and relapse of bowel or colorectal cancer, and may open the door to new diagnostic tools and treatment ideas, concluded researchers of a Spanish-led study published online in Cell Stem Cell this week.
Led by Eduard Batlle from the Catalan Institution for Research and Advanced Studies (ICREA), the researchers found that colorectal cancer cells trigger a set of genes that are similar to those found in intestinal stem cells.
They suggest colorectal cancer patients undergo genetic tests of the lining of their intestines to predict their chances of relapse.
Colorectal cancer causes hundreds of thousands of death worldwide every year.
Current treatment normally comprises surgery and chemotherapy, and most patients don’t relapse, but for nearly 40%, relapse occurs within months or years, with the cancer often spreading to other parts of the body.
Batlle said this suggests there are cells in the tumors that regenerate the disease, “but we still know very little about the biological reasons why”.
Intestinal stem cells are a type of non-specialized cell that give rise to all the cells in the intestines. They can produce up to 5 grams of intestinal epithelial cells, the type that form the lining of the intestines, every day.
For the study, Batlle and colleagues compared activated genes in cells in healthy intestines (both specialized cells and stem cells), with activated genes in tumor cells taken from patients with colorectal cancer.
They found that the activated genes in the tumor cells were similar to the activated genes in the stem cells, and the more activated genes they had in common, the higher the chance that the patient’s cancer would spread and relapse.
They also found that the activated genes in the tumor that were similar to the ones in the stem cells were in a subset of tumor cells that they called “tumor stem cells”.
When they transplanted these tumor stem cells into lab mice, tumors grew.
The findings support a growing idea that a hierarchical organization controls the growth of cancer, such that only “tumor stem cells” have the ability to start and propagate it.
Also, the ability of stem cells to renew indefinitely confers advantage to tumors. And because stem cells can survive for years, unlike specialized cells such as those found in the lining of the intestines that only live for a few days, or at the most, a few months, there is greater opportunity for their DNA to accumulate damage and become cancerous.
Discovering a link between intestinal stem cells and propagation of cancer is a breakthrough because it offers new avenues for predicting risk of relapse, for which there are very few clinical tools.
The idea that cancers require specific types of cell in order to develop and thrive, has already been shown in other cancers like breast cancer, gliomas (tumors that start in the brain or spine), and some types of lymphoma.
This study now adds another type of cell, the tumor stem cell, to that list.
“The Intestinal Stem Cell Signature Identifies Colorectal Cancer Stem Cells and Predicts Disease Relapse.”
Anna Merlos-Suárez, Francisco M. Barriga, Peter Jung, Mar Iglesias, María Virtudes Céspedes, David Rossell, Marta Sevillano, Xavier Hernando-Momblona, Victoria da Silva-Diz, Purificación Muñoz, Hans Clevers, Elena Sancho, Ramón Mangues, and Eduard Batlle.
Cell Stem Cell published early online 17 March 2011
DOI:10.1016/j.stem.2011.02.020
Additional source: IRB Barcelona.
Written by: Catharine Paddock, PhD