Fibroid Tumors Lack Crucial Structural Protein
Fibroid tumors the sometimes painful uterine growths affecting
many American women lack a key protein that plays a role in holding
tissues together, according to a study by researchers from the Uniformed
Services University of the Health Sciences (USUHS) and the National
Institute of Child Health and Human Development of the National
Institutes of Health.
"This finding is a major step in understanding the nature of
fibroids and may prove useful in efforts to devise more effective
treatments for them," said Duane Alexander, M.D., Director
of the NICHD.
The study has been published on line at http://www3.interscience.wiley.com/cgi-bin/jhome/38250
and will appear in the July 2004 issue of Genes, Chromosomes
Specifically, the researchers discovered that fibroids have low
levels of the protein dermatopontin. The protein is a key component
of the extracellular matrix the elastic meshwork of collagen and
other proteins that keeps cells in place. Moreover, the researchers
learned that another type of growth, keloids, also lack dermatopontin.
Keloids are an overgrowth of thick scar tissue that can form on
the skin after a cut or other wound heals. Both keloids and fibroids
disproportionately affect African Americans.
Fibroids, also known as leiomyomas, are noncancerous growths that
develop in the myoemetrium, the smooth muscle tissue of the uterus,
explained William Catherino, M.D., Ph.D, of NICHD's Pediatric and
Reproductive Endocrinology Branch.
Women with fibroids may experience painful menstrual periods, pain
during sexual intercourse, infertility, urinary and fecal incontinence,
and bowel obstruction, Dr. Catherino said. They are also more likely
to go into labor prematurely and to experience a miscarriage.
Dr. Catherino added that it's difficult to know exactly how many
women in the United States have fibroids, because in many cases
fibroids do not cause symptoms, he said. Some studies using ultrasound
have indicated that 70 to 80 percent of women may have the growths
but do not experience any problems from them. About one out of every
2 to 4 women will have symptoms from fibroids at some point during
their reproductive years. For women who experience severe symptoms,
treatment often involves surgery. In one form of surgery, myomectomy,
the fibroids are removed from the wall of the uterus. In many cases,
the fibroids return after surgery or their removal results in the
formation of painful scar tissue.
In other cases, the number of fibroids is so great that hysterectomy
(removal of the uterus) must be performed. According to the Centers
for Disease Control and Prevention, fibroids are the single greatest
reason for hysterectomy, accounting for 27 percent of the 650,000-675,000
hysterectomies performed in the United States each year.
In the study, researchers used a technique known as microarray
analysis to determine the activity levels of genes in fibroid tumors.
They examined both fibroid tissue and normal uterine tissue from
11 women who underwent hysterectomy as a treatment for fibroid symptoms.
They also examined samples of keloid tissue provided by another
The researchers found that the fibroid tissue had lower levels
of dermatopontin than did the normal uterine tissue. They also discovered
that keloid tissue had low levels of dermatopontin. Both the fibroid
tissue and the keloid tissue contained disorganized, unstructured
strands of collagen, Dr. Catherino said. In normal tissues, collagen
forms discrete strands.
Dr. Catherino and his colleagues suspect that fibroid tumors have
a genetic basis. Moreover, the same genetic factors that may predispose
African American women to develop fibroids may also play a role
in African Americans' predisposition toward keloids. He and his
coauthors wrote that African American women are 3.3 times more likely
to develop fibroids than are Caucasian American women and 3 times
more likely to develop keloids than are Caucasian American women.
Other evidence also points to a genetic basis for fibroids. Women
whose mothers, sisters or daughters have fibroids are more likely
to have fibroids themselves. Similarly, women with the genetic disorders
Alport Syndrome and Reed Syndrome are more likely than other women
to have fibroids.
Dr. Catherino hypothesizes that dermatopontin plays a role in preventing
the muscle cells of the uterus known as myometrial cells from developing
into another type of cell. Dermatopontin appears to react with the
integrin receptor on myometrial cells. Like a key fits into a lock,
molecules interact with cell receptors to bring about changes in
the cell. The integrin receptor and molecule appear to be important
for influencing the type of cell that a cell will become.
Dr. Catherino suspects that a failure of dermatopontin to interact
with the integrin receptor results in the cell losing its function
as a myometrial cell and becoming more like a fibroblast a type
of skin cell that produces collagen. In fact, the individual cells
in fibroids are referred to as myofibroblasts, because they have
characteristics of both myometrial cells and fibroblasts.
Additional information about fibroids is available from the NICHD
publication, Uterine Fibroids. This publication, along with other
NICHD publications, is available on the NICHD Web site, http://www.nichd.nih.gov,
or from the NICHD Information Resource Center, 1-800-370-2943; e-mail
The NICHD is part of the National Institutes of Health (NIH), the
biomedical research arm of the federal government. NIH is an agency
of the U.S. Department of Health and Human Services.