Lani
04-14-2011, 06:27 AM
NOW THEY HAVE TO FIGURE OUT WHY IT SOMETIMES DOESN'T WORK AND HOW TO REVERSE THAT
# Berkeley Lab Scientists Find that Normal Breast Cells Help Kill Cancer Cells
[Lawrence Berkeley National Laboratory]
It is well known that the human body has a highly developed immune system to detect and destroy invading pathogens and tumor cells. Now, researchers at the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) have shown that the body has a second line of defense against cancer - healthy cells. A new study shows that normal mammary epithelial cells, as they are developing, secrete interleukin 25, a protein known for its role in the immune system's response to inflammation, for the express purpose of killing nearby breast cancer cells.
"We found that normal breast cells provide an innate defense mechanism against cancer by producing interleukin 25 (IL25) to actively and specifically kill breast cancer cells," says breast cancer authority Mina Bissell, of Berkeley Lab's Life Sciences Division, who led this research. "This suggests that IL25 receptor signaling may provide a new therapeutic target for the treatment of breast cancer."
The results of this research are reported in the journal Science Translational Medicine in a paper titled "IL25 Causes Apoptosis of IL25R-expressing Breast Cancer Cells Without Toxicity to Nonmalignant Cells." Co-authoring the paper with Bissell were Saori Furuta, Yung-Ming Jeng, Longen Zhou, Lan Huang, Irene Kuhn and Wen-Hwa Lee, of the University of California, Irvine, who along with Bissell is a corresponding author.
Although cancer remains a leading cause of premature death in the world today, most people live cancer-free lives for decades. In fact, the rate of cancer disease in the human population is surprisingly low given that the cells in our bodies are exposed on a daily basis throughout our lifetimes to radiation and chemical damage, plus a host of other factors that promote harmful DNA mutations and malignant tumors. It is not as if mutant cells are not being generated, explains Saori Furuta, lead author of the Science Translational Medicine paper and a Berkeley Lab colleague of Bissell's.
"Even healthy individuals produce genetically impaired cells at the rate of up to 1,000 aberrant cells per day, however, as a part of homeostatic regulations, these cancer-prone cells are efficiently eradicated by the so- called tumor surveillance system of our body," Furuta says. "A number of tumor surveillance mechanisms have been described in the past, including the classic molecular tumor suppressors, immune surveillance, and suppression by the extracellular matrix and other microenvironmental factors. We are now adding a new type of tumor suppression to this list, IL25 and other proteins secreted by normal breast cells that kill or subdue their mutated neighbors."
In their study, Furuta, Bissell, Lee and their colleagues found that whereas IL25 was highly toxic to breast cancer cells, it did not harm normal breast cells. The selectivity, they discovered, is due to the presence of an abundance of exposed IL25 receptors on breast cancer cells. These IL25 receptors were absent on normal breast cells.
"Since IL25 is produced by healthy breast tissue as a natural defense mechanism against cancer during the cell differentiation process, we should be able to utilize IL25/IL25 receptor signaling as an organic approach to breast cancer therapy," Furuta says.
# ABSTRACT: IL-25 Causes Apoptosis of IL-25R-Expressing Breast Cancer Cells Without Toxicity to Nonmalignant Cells
[Science Translational Medicine]
As cells differentiate into tissues, the microenvironment that surrounds these cells must cooperate so that properly organized, growth-controlled tissues are developed and maintained. We asked whether substances produced from this collaboration might thwart malignant cells if they arise in the vicinity of normal tissues. Here, we identified six factors secreted by nonmalignant mammary epithelial cells (MECs) differentiating in three-dimensional laminin-rich gels that exert cytotoxic activity on breast cancer cells. Among these, interleukin-25 (IL-25/IL-17E) had the highest anticancer activity without affecting nonmalignant MECs. Apoptotic activity of IL-25 was mediated by differential expression of its receptor, IL-25R, which was expressed in high amounts in tumors from patients with poor prognoses but was low in nonmalignant breast tissue. In response to IL-25, the IL-25R on the surface of breast cancer cells activated caspase-mediated apoptosis. Thus, the IL-25/IL-25R signaling pathway may serve as a new therapeutic target for advanced breast cancer.
# Berkeley Lab Scientists Find that Normal Breast Cells Help Kill Cancer Cells
[Lawrence Berkeley National Laboratory]
It is well known that the human body has a highly developed immune system to detect and destroy invading pathogens and tumor cells. Now, researchers at the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) have shown that the body has a second line of defense against cancer - healthy cells. A new study shows that normal mammary epithelial cells, as they are developing, secrete interleukin 25, a protein known for its role in the immune system's response to inflammation, for the express purpose of killing nearby breast cancer cells.
"We found that normal breast cells provide an innate defense mechanism against cancer by producing interleukin 25 (IL25) to actively and specifically kill breast cancer cells," says breast cancer authority Mina Bissell, of Berkeley Lab's Life Sciences Division, who led this research. "This suggests that IL25 receptor signaling may provide a new therapeutic target for the treatment of breast cancer."
The results of this research are reported in the journal Science Translational Medicine in a paper titled "IL25 Causes Apoptosis of IL25R-expressing Breast Cancer Cells Without Toxicity to Nonmalignant Cells." Co-authoring the paper with Bissell were Saori Furuta, Yung-Ming Jeng, Longen Zhou, Lan Huang, Irene Kuhn and Wen-Hwa Lee, of the University of California, Irvine, who along with Bissell is a corresponding author.
Although cancer remains a leading cause of premature death in the world today, most people live cancer-free lives for decades. In fact, the rate of cancer disease in the human population is surprisingly low given that the cells in our bodies are exposed on a daily basis throughout our lifetimes to radiation and chemical damage, plus a host of other factors that promote harmful DNA mutations and malignant tumors. It is not as if mutant cells are not being generated, explains Saori Furuta, lead author of the Science Translational Medicine paper and a Berkeley Lab colleague of Bissell's.
"Even healthy individuals produce genetically impaired cells at the rate of up to 1,000 aberrant cells per day, however, as a part of homeostatic regulations, these cancer-prone cells are efficiently eradicated by the so- called tumor surveillance system of our body," Furuta says. "A number of tumor surveillance mechanisms have been described in the past, including the classic molecular tumor suppressors, immune surveillance, and suppression by the extracellular matrix and other microenvironmental factors. We are now adding a new type of tumor suppression to this list, IL25 and other proteins secreted by normal breast cells that kill or subdue their mutated neighbors."
In their study, Furuta, Bissell, Lee and their colleagues found that whereas IL25 was highly toxic to breast cancer cells, it did not harm normal breast cells. The selectivity, they discovered, is due to the presence of an abundance of exposed IL25 receptors on breast cancer cells. These IL25 receptors were absent on normal breast cells.
"Since IL25 is produced by healthy breast tissue as a natural defense mechanism against cancer during the cell differentiation process, we should be able to utilize IL25/IL25 receptor signaling as an organic approach to breast cancer therapy," Furuta says.
# ABSTRACT: IL-25 Causes Apoptosis of IL-25R-Expressing Breast Cancer Cells Without Toxicity to Nonmalignant Cells
[Science Translational Medicine]
As cells differentiate into tissues, the microenvironment that surrounds these cells must cooperate so that properly organized, growth-controlled tissues are developed and maintained. We asked whether substances produced from this collaboration might thwart malignant cells if they arise in the vicinity of normal tissues. Here, we identified six factors secreted by nonmalignant mammary epithelial cells (MECs) differentiating in three-dimensional laminin-rich gels that exert cytotoxic activity on breast cancer cells. Among these, interleukin-25 (IL-25/IL-17E) had the highest anticancer activity without affecting nonmalignant MECs. Apoptotic activity of IL-25 was mediated by differential expression of its receptor, IL-25R, which was expressed in high amounts in tumors from patients with poor prognoses but was low in nonmalignant breast tissue. In response to IL-25, the IL-25R on the surface of breast cancer cells activated caspase-mediated apoptosis. Thus, the IL-25/IL-25R signaling pathway may serve as a new therapeutic target for advanced breast cancer.