Ovarian Cancer May Arise From Stem-Like Cells
The researchers, from Cornell University and Cold Spring Harbor Laboratory (CSHL), both in New York, write about their discovery in the 6 March online issue of Nature.
The previously unknown stem-like cells sit in niches in the epithelium tissue of ovaries and are thought normally to repair small tears that form when eggs are produced.
Epithelial tissue is the most prolific of the four main types of tissue in the body (the other three being muscle, nerve and connective tissue). It is made of tightly packed cells, and lines the cavities of the body and also covers flat surfaces.
In their background information the authors explain how epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths among women in the United States, yet we don't know very much about how the cells in this part of the body become cancerous.
Co-author Grigori Enikolopov, who led the CSHL team, summarizes their discovery in a press statement:
"We demonstrated that a stem cell population sits in a portion of the ovary called the hilum, and can repair the ruptures of the ovarian tissue during ovulation, and that these cells are easily transformed into tumor cells."
More and more researchers are coming to the conclusion that cells that are stem-like, that is cells that have not yet fully differentiated and retain some potential to become one of a number of cell-types, can spontaneously mutate to become cancerous and seed a tumor.
Epithelial cancers like those of the ovary and the bowel are known to begin in the transition region between different types of epithelial cells.
Researchers have proposed that cells in these transition regions are less differentiated, but until this study, there was little evidence to support this.
In their study, Enikolopov and colleagues found a group of epithelial cells in the mouse ovary's hilum region that proliferate slowly and can renew themselves. These cells also express high levels of a known stem-cell marker, aldehyde dehydrogenase (ALDH1).
The team took some of these hilum epithelial cells, switched off two tumor suppressor genes, and then transplanted them into eight female mice.
Seven of the mice developed ovarian tumors that spread.
The tumor suppressor genes that they switched off are called Trp53 and Rb1. These same genes are known to frequently mutate in human ovarian cancers.
The authors conclude:
"Our study supports experimentally the idea that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas."
They suggest that by identifying such a niche in the ovarian surface epithelium, the study may have "important implications" for understanding how epithelial ovarian cancer develops.
Enikolopov says the findings may also help us understand how cancers develop in the uterine cervix and the esophagus, and other parts of the body that have similar epithelial transition/junction areas.
"Now we know what sort of cells to look for," he adds.
Funds from the National Institutes for Health, the National Cancer Institute, New York State Stem Cell Science (NYSTEM), the Marsha Rivkin Center for Ovarian Cancer Research, the Russian Ministry of Education and Science, and the Cornell Comparative Cancer Biology Training Program, helped finance the study.
In 2012, researchers at Moffitt Cancer Center in Florida reported finding that the micro ribonucleic acid miR-214 plays a critical role in regulating ovarian cancer stem cell properties.
Written by Catharine Paddock PhD