June 8, 2011 Researchers at Children's Hospital Boston have found a marker called ABCB5 that both tags a small proportion of cells within colorectal cancers and fuels resistance in those cells to standard treatments. The results indicate that eliminating ABCB5-expressing cells is crucial for successful colorectal cancer treatment, while adding to the growing body of evidence for a theory of cancer growth called the cancer stem cell hypothesis.
An international team led by Brian J. Wilson, PhD, Tobias Schatton, PhD, and Markus Frank, MD, of the Transplantation Research Center at Children's Hospital Boston, and Natasha Frank, MD, of the VA Boston Healthcare System and Brigham and Women's Hospital, and colleagues at the University of Wurzburg in Germany reported the findings online in the journal Cancer Research on June 7, 2011.
An estimated 141,000 Americans will be diagnosed with colorectal cancer this year. While its mortality has been dropping over the last two decades thanks to screening and improved treatment options, colorectal cancer is still the second leading cause of cancer-related death in the United States.
Recognizing ABCB5's role as a marker of tumor recurrence in melanoma and liver cancer, and knowing from previous studies that the gene for ABCB5 is also active in colorectal cancer, the Franks' team studied the protein's expression in both normal and cancerous colorectal tissue specimens. They found that ABCB5 is found only rarely in healthy colorectal tissue, but is present at levels 23 times greater in cancerous tissue.
Underscoring its preferential expression on stem cells, ABCB5 was frequently accompanied on both healthy and cancerous cells by a second protein, CD133, which is thought to be a marker of both healthy intestinal stem cells and colorectal cancer stem cells. CD133 is also associated with aggressiveness in colorectal cancer.
To understand ABCB5's role in treatment resistance, the
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Children's Hospital Boston