Researchers discovered a gene involved in the spread of breast cancer, which may lead to new treatments for a disease that kills about 1 in 35 women.
The gene, called metadherin, may be crucial to cancer’s spread because it helps tumor cells stick to blood vessels in distant organs, researchers at Princeton University and the Cancer Institute of New Jersey found. The gene also makes tumors more resistant to drugs used to wipe out deadly cells.
Breast cancer is the most frequently diagnosed malignancy in U.S. women, excluding cancer of the skin, according to the American Cancer Society. Determining the genetic mechanism involved in the disease’s spread, known as metastasis, may help answer one of the biggest mysteries in cancer research.
“Inhibiting this gene in breast cancer patients will simultaneously achieve two important goals -- reduce the chance of recurrence and, at the same time, decrease the risk of metastatic dissemination,” Yibin Kang, an assistant professor of molecular biology at Princeton who led the research, said in a statement on the Cancer Institute’s Web site. “These are the two major reasons why breast cancer patients die from the disease.”
The finding, published today in Cancer Cell, is based on three years of work, using an approach that combines the emerging science of integrative genomics with the classical methods of clinical research and laboratory experiments, the authors said.
Quick Spread
Breast cancer is caused by a malignant tumor that develops from cells in the breast. The most common sign of breast cancer is a new lump or mass in the breast. Scientists once thought that breast cancer spread first to nearby tissue and underarm lymph nodes before reaching other parts of the body. They now believe cancer cells may break away from the primary tumor in the breast even when the disease is in an early stage.
After re-analyzing clinical breast cancer databases and tumor samples collected from patients, the researchers found an area of human chromosome 8 called 8q22 is repeated multiple times in the genomes of potentially lethal breast tumors. Most normal DNA sequences contain only two copies of a given gene, conveyed from the genomes of the male and female parents.
The researchers went on to discover that among a handful of genes in the 8q22 region, metadherin, also known as MTDH, is responsible for the aggressive behavior of some tumors. The scientists found that tumors which over-express MTDH are more likely to spread to the lungs, other vital organs and bones. These tumors were also found to be more resistant to some chemotherapy agents.
“By analyzing 250 breast tumor samples from patients, we found that this gene is amplified and over-expressed in over 30 to 40 percent of breast cancer cases,” Kang said. “This indicates that new drugs against metadherin may potentially benefit a large population of breast cancer patients.”
The work was funded by a Department of Defense Era of Hope Scholar Award and grants from the National Institutes of Health, the American Cancer Society, the Susan G. Komen Foundation and the New Jersey Commission on Cancer Research.
Testicle Stem Cells Become Bone, Muscle in German Experiments
Stem cells were isolated from the testicles of adult men and turned into bone, muscle, neural and other kinds of cells, German researchers said.
The advance, reported today in the journal Nature, may provide an alternative way to generate powerful stem cells that might be used to repair or replace damaged tissue in male patients with hard-to-treat diseases. Currently, scientists create stem cells by extracting them from embryos or genetically manipulating adult cells to make them pluripotent, or able to become many other cell types.
The use of testicle cells may also represent a new way to make lines of cells from a male with an inherited disease, for the purpose of studying his condition at the cellular level and testing drugs that might be effective in treating it.
The work by Thomas Skutella, director of the Center for Regenerative Biology and Medicine, in Tuebingen, Germany, produced a ``breathtaking result,'' said George Daley, a researcher at the Harvard Stem Cell Institute and at Children's Hospital Boston. While scientists had known that mouse testes give rise to other cells, he said, it wasn't clear that such cells could be isolated from humans.
``These are the only pluripotent cells present in adult human organisms,'' Skutella said. With this method, he said, ``you could take biopsies from people with Parkinson's or any kind of inherited disease'' and study the cells to learn how they function and respond to drugs.
The technique, if confirmed and improved, may allow researchers to sidestep ethical controversies that have dogged the field since University of Wisconsin scientists isolated stem cells from human embryos a decade ago.
Embryo Research Decried
Critics of embryonic research, including the Catholic Church, U.S. President George W. Bush and German lawmakers, view embryo destruction as immoral. Bush banned federal funding of research that uses newly destroyed embryos. German authorities went further, barring researchers there from creating embryonic stem cells, although they can import those derived in other countries, Skutella said.
Another method, developed two years ago by Japanese researchers, uses genes and viruses to reprogram adult skin cells so they become pluripotent and behave like embryonic stem cells. While this method avoids using embryos, the technique may trigger cancer or other unwanted effects. More recently researchers have begun to refine this method by eliminating viruses linked to cancer.
One advantage of Skutella's method is that if a man's own cells were used to make a therapy, they could be used to treat him without fear that his body would reject the cells. While he was able to coax the testicular stem cells to turn into a number of cell types, he wasn't able to make still other types, including heart cells.
Testicles Donated
Skutella and his colleagues obtained testicular tissue from various sources, including organ donors who had died. Others who supplied tissue were being treated for infertility or had their testicles removed in the course of surgery to change their sex to female or to treat prostate cancer.
The scientists used a complex process to identify and isolate a type of precursor cell that normally helps make sperm. They then concocted a chemical cocktail that allowed them to expand the stem cells.
The advance, reported today in the journal Nature, may provide an alternative way to generate powerful stem cells that might be used to repair or replace damaged tissue in male patients with hard-to-treat diseases. Currently, scientists create stem cells by extracting them from embryos or genetically manipulating adult cells to make them pluripotent, or able to become many other cell types.
The use of testicle cells may also represent a new way to make lines of cells from a male with an inherited disease, for the purpose of studying his condition at the cellular level and testing drugs that might be effective in treating it.
The work by Thomas Skutella, director of the Center for Regenerative Biology and Medicine, in Tuebingen, Germany, produced a ``breathtaking result,'' said George Daley, a researcher at the Harvard Stem Cell Institute and at Children's Hospital Boston. While scientists had known that mouse testes give rise to other cells, he said, it wasn't clear that such cells could be isolated from humans.
``These are the only pluripotent cells present in adult human organisms,'' Skutella said. With this method, he said, ``you could take biopsies from people with Parkinson's or any kind of inherited disease'' and study the cells to learn how they function and respond to drugs.
The technique, if confirmed and improved, may allow researchers to sidestep ethical controversies that have dogged the field since University of Wisconsin scientists isolated stem cells from human embryos a decade ago.
Embryo Research Decried
Critics of embryonic research, including the Catholic Church, U.S. President George W. Bush and German lawmakers, view embryo destruction as immoral. Bush banned federal funding of research that uses newly destroyed embryos. German authorities went further, barring researchers there from creating embryonic stem cells, although they can import those derived in other countries, Skutella said.
Another method, developed two years ago by Japanese researchers, uses genes and viruses to reprogram adult skin cells so they become pluripotent and behave like embryonic stem cells. While this method avoids using embryos, the technique may trigger cancer or other unwanted effects. More recently researchers have begun to refine this method by eliminating viruses linked to cancer.
One advantage of Skutella's method is that if a man's own cells were used to make a therapy, they could be used to treat him without fear that his body would reject the cells. While he was able to coax the testicular stem cells to turn into a number of cell types, he wasn't able to make still other types, including heart cells.
Testicles Donated
Skutella and his colleagues obtained testicular tissue from various sources, including organ donors who had died. Others who supplied tissue were being treated for infertility or had their testicles removed in the course of surgery to change their sex to female or to treat prostate cancer.
The scientists used a complex process to identify and isolate a type of precursor cell that normally helps make sperm. They then concocted a chemical cocktail that allowed them to expand the stem cells.
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