Stem cells are an important focus in cancer research, as recent studies have revealed that these specialized cells may be involved in tumor growth, including colon cancer. Briefly, colon tissue layers have specific compartments (called “crypts”) that are home to several different types of cells, including stem cells. Small numbers of stem cells reside at the base of these crypts, producing new cells that begin as
proliferating cells, which change into differentiating cells as they travel up the crypt to replace older dying cells (apoptotic cells). This is a normal, healthy process that occurs in all of the body’s tissues. However, if this process goes awry, the stem cells can continuously produce an excess number of malignant cells,
resulting in a tumor.
Though colon cancer is well understood from a genetic perspective, current therapies have not been fully able to eradicate it in advanced stages. Although many therapies are able to shrink tumors, patients with advanced colorectal cancer will often have a recurrence. Recent discoveries have shown that these recurrences may be due, in part, to cancer stem cells, because stem cells do not seem to be affected by conventional therapies. Just how these cells are able to continue producing new tumor cells is a mystery. Fortunately, researchers are starting to better understand this process, and have proposed that cancer stem cells may be the missing link to the puzzle of why some cancer recurs despite aggressive treatment.
|Depiction of Colorectal Stem Cells - from the colonic epithelium to the individual colonic crypt.|
Two recent studies have shown that cancer stem cells, and not “traditional” cancer cells, are responsible for initiating, organizing and maintaining colorectal tumor formation. (Traditional cancer cells are those that make up the bulk of the tumor). In these studies, scientists transplanted both
cancer stem cells and traditional cancer cells from colon tumors into healthy mice. They observed that in those animals who received the colon cancer stem cells, colon tumors quickly formed, whereas
virtually no tumors formed in the animals which received the traditional colon cancer cells. In a related study, researchers clarified just how cancer stem cells are able to cause the formation of tumors.
Studies were peformed on the intestines of mice in which a specific tumor suppressor gene had been deleted. In these tissues where the gene was deleted, they discovered that stem cells actually change position and increase in number, resulting in intestinal polyposis.
Researchers from all three studies reached the conclusion that colon cancer tumors may develop from a small number of so-called “cancer stem cells,” which readily promote tumor development. These cancer stem cells are distinct from the traditional cancer cells that make up the bulk of the tumor and are more active than normal stem cells. Such discoveries help scientists to understand that a tumor is made up of a hierarchy of different cells, much like every other part of the body. The researchers also concluded that it might someday be possible to identify the unique genetic properties of colon cancer stem cells, enabling scientists to design drugs to target only those cells. Ideally, these treatments would prevent damage to healthy cells and may be a better way to stop the disease. Dr. John Dick from the Ontario Cancer Institute compared combating cancer to killing a backyard weed: “You can keep cutting the leaves off the weed, but the weed will re-grow. But if you cut the roots, the leaves will wither away. Killing the cancer stem cells is the equivalent of killing the root of the weed.”
“Identification and expansion of human and colon-cancer initiating cells.” Nature. January 4, 2007. 445(7123): 111-5.
“A human colon cancer cell capable of initiating tumour growth in immunodeficient mice.” Nature. January 4, 2007. 445(7123): 106-10.
PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nature Genetics. January 21, 2007. 39(1). Published online.