New understanding of molecular changes that convert harmless cells surrounding ovarian cancer cells into cells that promote tumor growth and metastasis provides potential new therapeutic targets for this deadly disease, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.
"New approaches for treating patients with ovarian cancer are desperately needed," said Ernst Lengyel, M.D., Ph.D., professor in the department of obstetrics and gynecology at the University of Chicago. "There have been no new approaches introduced into the clinic for quite some time, and we have seen no major improvements in patient survival over the years."
According to Lengyel, greater understanding of the biology of ovarian cancer should provide new therapeutic targets. He and his colleagues set out to learn how normal stromal cells are transformed into cancer-associated fibroblasts, which are found in the tissue immediately surrounding the ovarian cancer cells. Intimate cross talk between cancer-associated fibroblasts and cancer cells boosts tumor growth and metastasis.
"The strength of our study lies in the fact that we used cells from patients, rather than cell lines," said Lengyel. "This means that our model system reflects as closely as possible the clinical situation in patients."
Initial analysis indicated that cancer-associated fibroblasts from patients with ovarian cancer had altered patterns of expression of small molecules called microRNAs compared with normal and tumor-adjacent fibroblasts.
MicroRNAs are important regulators of gene expression because they help direct that cell's function. Thus, modified patterns of microRNA expression change cell function.
Lengyel and colleagues further studied the microRNA most upregulated in cancer-associated fibroblasts and the two microRNAs most significantly downregulated. When they changed the pattern of expression of these three microRNAs in normal fibroblasts to mimic the pattern they had seen in cancer-associated fibroblasts, they found that the normal fibroblasts were converted into cells with in-vitro characteristics of cancer-associated fibroblasts. Moreover, the cells reprogrammed to become cancer-associated fibroblasts by altering microRNA expression enhanced the growth of tumor cells in a mouse model of ovarian cancer.
Conversely, restoring the pattern of expression of the three microRNAs to normal in cancer-associated fibroblasts reduced their cancer-promoting characteristics.
"Therapeutic approaches targeting microRNAs in cancer cells are under development," said Lengyel. "Our work suggests that it might be possible to modify microRNA expression in cancer-associated fibroblasts for therapeutic benefit."
Lengyel added that treatments targeting microRNAs in cancer-associated fibroblasts may be particularly effective because these cells are genetically stable, unlike cancer cells, therefore, the risk that cancers will become unresponsive to these treatments is less than for treatments targeting cancer cells.
American Association for Cancer Research: http://www.aacr.org
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Institute for Highway Safety is known for crash-test safety ratings, but as cars get smarter there's a need to look beyond crashworthiness
Researchers have long struggled to resolve what happens to information when it falls inside a black hole, but the famous physicist says he has a solution
Researchers have been using muons to take a peek inside the nuclear reactors in Japan that melted down in 2011. The results could aid the continuing cleanup operations.
Neutrinos, created by violent phenomena such as black holes and exploding stars, could hold the key to the universe’s most distant and mysterious events
Better MRI scanners could result from a trick in which a magnetic field springs up from nowhere, using materials famous for their link to invisibility cloaks
Water locked away in rocks for 1.5 billion years reveals conditions were right for complex organic molecules to form in deep sea hydrothermal vents
Helium, used in nuclear, medical and, yes, party industries, has become scarce, but new research has revealed a possible way to pinpoint fresh sources
New lab results show how collisions between comets and planets can make the molecules that are the essential building blocks of life.
A startup company says it is expanding the language of DNA to create new tools for drug discovery.
If scientists can convince people to use the app, they hope it will help them solve a cosmic mystery. This story originally aired on March 27, 2015 on All Things Considered.