Mother-child bond may help prevent cancer
Dr. John Lister and Dr. Gary Gilmore of West Penn Hospital led research that points to a possible advantage from fetal cells remaining in a mother's body long after giving birth.
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Mothers have many reasons for loving their sons.
But one blessing they probably don't know about is the cells their sons gave them when they were in the womb.
It's part of a process known as fetal microchimerism, in which the mother and fetus exchange certain cells during pregnancy that live on in each other's bodies for years and years.
And now, researchers at the Western Pennsylvania Cancer Institute at West Penn Hospital have found that fetal cells that mothers got from their sons may protect them against cancer.
In a study published recently in the journal Experimental Hematology, a group led by Gary Gilmore and John Lister found evidence of fetal cells in the blood of 57 percent of women who had given birth to a son and were cancer-free, but in only 34 percent of women with sons who had cancer.
That bolsters earlier studies by Vijaykrishna K. Gadi at the Fred Hutchinson Cancer Research Center in Seattle, showing that women who had been diagnosed with breast cancer had much lower levels of male fetal cells in their bodies than women without cancer.
The term "microchimerism" -- pronounced micro-KIME-er-ism -- comes in part from the old Greek myth of the chimera, which Homer described as "a thing of immortal make, not human, lion-fronted and snake behind, and a goat in the middle."
The studies suggest, though, that this chimera is not horrible and alien, but natural and protective.
Although they have no direct proof yet, all three doctors said this month that they believe the male cells may have an advantage in detecting and attacking cancer cells growing in their mothers' bodies because they come from a different immune system.
On the one hand, the fetal and maternal cells are enough alike that they don't usually attack each other, said Dr. Lister, a West Penn cancer specialist, but on the other hand, the fetal cells are different enough that they may be able to better recognize and go after any cancer cells.
The discovery may one day lead to new cancer treatments, the doctors said.
One approach would be to give female cancer patients white blood cells from their adult sons, to see if that would boost their cancer defenses, Dr. Lister and Dr. Gilmore said. The two have designed a trial to test that theory, but have not yet recruited patients for it.
Another technique, Dr. Gadi said, would be to find ways to stimulate the fetal cells that are already in a mother's bloodstream, much the way that a vaccine boosts a person's own immune system.
At the very least, Dr. Gadi added, figuring out the proportion of male fetal cells in a mother's bloodstream may help determine how potent her treatment would need to be if she gets cancer.
Mothers may get the same cancer protection from fetal cells from their daughters, the doctors said, but it's much harder to detect those cells at present.
Doctors can find male fetal cells by amplifying DNA fragments from the male Y chromosome found in the mother's blood. The tests to find a daughter's fetal cells, though, are much more challenging and have been used in only a few centers nationally to date.
While doctors don't have direct proof that fetal cells protect against cancer, they have indirect evidence from previous cancer treatments.
The notion that a woman's own immune cells are not very good at fighting off cancer is borne out by the many failed attempts at trying to develop cancer vaccines from a patient's own tumors. Dr. Lister said.
On the other hand, one of the most effective cancer treatments today is bone marrow transplants, and that's largely because immune cells from the donor seek out and destroy the recipient's tumor cells, the doctors said.
"It's this greater degree of difference that allows the immune system of the transplanted cells to kind of ramp up and see the differences" in a patient's cancer cells, said Dr. Gilmore, director of the cancer institute's hematopoiesis research program.
So fetal cells may be just enough different from the mother's immune system that they can lower the boom on newly formed cancer cells.
In some cases, the differences in fetal cells may backfire, though.
In work her lab pioneered in the 1990s, J. Lee Nelson of the Fred Hutchinson center found that women who had more fetal cells in their tissue were also more likely to get autoimmune diseases like scleroderma or rheumatoid arthritis.
Dr. Gadi, who worked with Dr. Nelson on that research, said their current hypothesis is that in those cases, the maternal cells are reacting against the fetal cells, and that once the immune system is turned on in that way, it is like a runaway train that can't easily be stopped.
Dr. Gadi's view of the role of fetal cells is that "If you turn up that switch [on fetal cells] too far, then you cause trouble with autoimmune reactions, but if you turn it down too far, you get more cancers."
The emerging interest in fetal microchimerism is part of an older, larger mystery -- how women are able to carry separate creatures in their bodies for nine months without rejecting them.
Of course, fetuses share half their genes with their mothers. On top of that, Dr. Gadi said, the mother's immune system seems to change during pregnancy to dampen down any reaction against the fetus, while the "fetus itself is actively saying to the mother, 'Don't attack me, don't attack me.' "
The whole process is an amazing instance of biological restraint, Dr. Lister said. "Normally, if anything invades us, we have white blood cells that will mount a profound attack and usually kill the invading organism, whether that be a bacterium, a virus, a parasite or even a transplanted organ. A mother carrying a fetus has a transplanted organ that's growing within her that's foreign to her," and yet she tolerates it for months on end.
The place where mother and fetus meet is the placenta, part of which comes from each. Inside this organ, fetal blood vessels from the umbilical cord nestle near maternal blood vessels, and molecules can pass between them.
The mother routes nutrition, oxygen and antibodies from her immune system to the fetus, which sends waste and carbon dioxide back to her for disposal. In fact, the maternal antibodies comprise the main immune protection for newborns in the first few weeks of life.
The cells involved in fetal microchimerism, from both the fetus and the mother, last much longer, though, and may be present for most of a person's life.
The impact of maternal cells that live on in children hasn't been studied widely, but it may play a key role in bone marrow and organ transplants between siblings, Dr. Gilmore and Dr. Lister said.
Doctors already know that when they select siblings for transplant, it is more important to match the blood markers inherited from their father than from their mother. One reason for that may be that all siblings have already received maternal cells in the womb, so they wouldn't react to any of the maternal blood markers as being foreign.
At this point, scientists know that fetal microchimerism is real, but they are still trying to tease out all the consequences of it.
One thing researchers have learned, Dr. Gadi said, is that we can no longer be so certain where one person's identity ends and another's begins. "There's no fine line dividing our identities," he said. "It's completely intermingled."
It also adds new meaning to the bond between mothers and children, Dr. Gilmore said. "The old saw is that mothers are closer to their children because they carried them, and in a way that's actually true, because mom is carrying a little of you and you're carrying a little of mom for the rest of your lives."
First Published November 19, 2008 12:00 am