Scientists at St. Jude Children's Research Hospital have answered a central question in cancer biology: whether normal stem cells can give rise to tumors.
Stem cells are immature cells that can renew themselves and give rise to mature differentiated cells that compose the range of body tissues. In recent years, researchers have developed evidence that cancers may arise from mutant forms of stem cells.
Like a brand-name product instantly identifiable by its trademarked logo, normal and cancerous stem cells display on their surface characteristic proteins, including Prominin1 or CD133. A key question in cancer biology has been whether these so-called cancer stem cells arise from normal stem cells or more mature cancer cells that somehow reacquire the characteristics of stem cells.
In the advanced, online issue of the journal Nature, St. Jude investigators show that Prominin1 marks normal intestinal stem cells and that these cells, when mutated, give rise to intestinal tumors. The finding could also aid in identifying the source of cancer stem cells in the lung, kidney, brain, pancreas and other tissues.
"The idea that cancers might arise from mutant stem cells is an attractive one; but until now the link between normal and cancer stem cells in solid tissues like the intestine was not known," said Richard Gilbertson, M.D., Ph.D., associate member of the St. Jude Developmental Neurobiology and Oncology departments and the paper's senior author. "Our work provides the first direct link between normal solid tissue stem cells and cancer. The fact that this occurs in the intestine is particularly interesting since human intestinal tumors contain Prominin1-expressing cancer stem cells."
In addition to providing insights into the origins of cancer, the work might help scientists identify more effective treatments. "Normal stem cells are designed to withstand environmental insults," Gilbertson said. "Thus cancer stem cells might use these same mechanisms to resist chemotherapy and radiotherapy. Remnant cancer stem cells might therefore cause tumors to relapse and re-grow following treatment. If we could kill these cancer stem cells, we might be able to prevent relapse. Understanding the link between normal and cancerous stem cells should help us target the latter while preserving the former."