Berkeley Lab scientists identify why older women are more susceptible to breast cancer -
As women age, breast key cells ignore their environment, scientists at Berkeley Lab find
DFO scientists at the Lawrence Berkeley National Laboratory of energy (Berkeley Lab) have won more ideas in which older women are more susceptible to breast cancer. They found that women age, the cells responsible for maintaining healthy breast tissues stop responding to their immediate surroundings, including mechanical signals, which should encourage them to suppress tumors nearby.
Their work highlights how aging alters cellular and molecular functions, and how these changes contribute to the prevalence of breast cancer in older women. The disease is most frequently diagnosed in women aged 55 to 64, according to the National Cancer Institute.
The research appears online June 5 in the journal Cell Reports . It was directed by Mark LaBarge of the Life Sciences Division of Berkeley Lab, with the help of first author Fanny Pelissier and other scientists from Berkeley Lab, and researchers from the University of Berkeley and the University Norwegian Bergen.
The scientists studied multipotent progenitor cells, a type of adult stem cells that is believed to be the origin of many breast cancers. There are two years, the group of LaBarge found that women age, multipotent progenitors accumulate in the epithelial tissues of the breast. They did not know why these cells increase in number, but they believed their microenvironment or the cellular tissue matrix surrounding the plays a role.
To explore this idea, the scientists examined samples of mammary epithelial human cells pre-menopausal women and post. They wanted to know how multipotent progenitors in these tissue samples are affected by tiny changes to their microenvironments. They placed the fabric on soft polymer surfaces that mimic breast normal tissues, as well as progressively more severe polymer surfaces that mimic the rigidity of a tumor.
They found that multipotent progenitors in tissue from women under 30 years are extremely sensitive to changes in their immediate environment. When the tissue of young women was placed on a soft polymer, differentiated multipotent progenitors in producing luminal cells of milk. When the fabric was placed on a rigid polymer, the cells have reduced production of luminal cells and accelerated production of tumor myoepithelial cells that fight.
"We think this is a defense mechanism. The tissue epithelia recognizes that the stiffness is not good and produces tumor suppressor," says LaBarge.
But this defense was not observed in the tissues of elderly women over 55. Instead of responding to a rigid polymer by upping the production of tumor suppression pluripotent progenitor cells from elderly women produced equal amounts of luminal and suppressor cell tumors. They also made more of themselves. This is bad for two reasons. The majority of cancers diagnosed in older women luminal, and multipotent progenitors means more cells that can become cancerous.
"We found that women age, multipotent progenitor cells, which are the cells responsible for maintaining healthy breast tissue homeostasis, no longer respond to their microenvironment as they do in younger women," LaBarge said.
"Our work shows that one reason for this is that multipotent progenitors in older tissues do not properly perceive the differentiation indices, such as the mechanical stiffness of their environment" adds it.
scientists traced this failure to a break in a cellular process. the process converts external mechanical signals, in this case, the rigidity of the tissue outside of the cell membrane, in a molecular internal message that tells the nucleus what to do. in multipotent progenitors in women aged 55 years, molecules that help to deliver that message are inefficiently activated, the scientists found.
They believe that this distribution comes from changes in the genes of the way women are activated and silenced as they grow.
Their functional analysis of multipotent progenitors was made possible by the co-author of work and Berkeley Lab scientist Martha Stampfer, who curated a large collection of samples of breast tissue there about 30 years. The specimens have allowed scientists to create a wide range of normal human mammary epithelial stem cells of women aged 16 to 91 years.
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