NOTE: This release was originally published by Michigan State University College of Human Medicine.
Uterine fibroid tumors are the leading cause of hysterectomies in the U.S., yet little is known about what causes them. A new study, however, has taken researchers one step closer to understanding how these tumors develop and grow.
Researchers at the Michigan State University College of Human Medicine, Van Andel Institute (VAI) and Spectrum Health have uncovered new information about the genes associated with the tumors, a breakthrough that eventually may lead to better treatments that could help many women to avoid surgery.
“This study could not have been done without that collaboration,” said Jose Teixeira, Ph.D., a professor in the college’s Department of Obstetrics, Gynecology and Reproductive Biology, who proposed the research.
The study, funded by the National Institutes of Health (NIH) and published in the journal Cell Reports, found that one of the genes they discovered associated with uterine fibroids, known as HOXA13, when activated, appeared to correlate with a transformation of cells in the muscle of the uterus into cells more typically found in the cervix – a process called “homeotic transformation.”
“It’s a cell type in a position where it doesn’t belong,” Teixeira said. “This was a surprise.”
That finding is significant, because further research could lead to new therapies to interrupt the molecular chain of events that cause the growth of fibroid tumors.
Teixeira, who has spent many years researching uterine fibroid tumors, recalled that a surgeon once asked him, “Why are you working on that? We have a cure. It’s called hysterectomy.”
But hysterectomy often is undesirable for women of reproductive age and carries risks for women of any age. An estimated 75 percent of reproductive-age women have uterine fibroids, and about 25 percent of them suffer symptoms, including pelvic pain, heavy menstrual bleeding, pregnancy loss and infertility. The occurrence and severity of symptoms is even higher among African American women.
A team led by Dave Chesla, MHA, director of research operations for Spectrum Health, collected fibroid tissue samples for the study while protecting the anonymity of the patients.
VAI researchers specialized in bioinformatics – a field that combines biology, computer science and statistics – analyzed the samples for their genetic characteristics.
“Collaboration is the key,” said Hui Shen, Ph.D., an associate professor at VAI who led the bioinformatics team crucial to unlocking the genetic secrets in the study. “These kinds of studies require multiple teams.” The collaboration was facilitated “because we are all within a mile of each other – the Medical Mile,” said Shen, who was assisted by postdoctoral fellow Huihui Fan, M.D., Ph.D..
The discovery that fibroid tumors have characteristics of cervical cells could be a key to better treatments, Teixeira said. For example, among pregnant women, the cervix typically softens just before delivery. Figuring out what causes the cervix to soften could suggest new therapies that soften the fibroid tumors and prevent or inhibit their growth, he said.
The disease “kind of flies under the radar,” attracting “a paucity of research,” said Chesla. The latest study was “a true collaboration,” he said, not only among the researchers, but by the patients who were willing to donate tissue samples.
“Without the patients, none of this happens,” he said, adding that “we hope this will lead to further research.”
In fact, it already has. The researchers are conducting a follow-up study also funded by the NIH.
“Is there a place where we can intervene?” Teixeira asked. “That’s the follow-up. If we can find out what’s causing the cervical softening, then we might be able to investigate treatment.”
And that could prevent the fibroid tumors from growing.
Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health under award R01HD072489 (PI Teixeira). The next phase of the project is expected to be supported by NICHD through award R01HD096259-01A1 (PI Teixeira). The content is solely the responsibility of the authors and does not necessarily represent the official views of any funding organization.
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