Free fatty acids in the blood appear to boost proliferation and growth of cancer cells, which could help explain obese women’s increased risk of developing breast cancer after menopause, research found.
Researchers at the University of Illinois obtained blood samples from a tissue bank and compared those of healthy women with the samples of women, who were healthy at outset but later developed breast cancer.
They also analyzed additional blood samples from 37 non-obese and 63 obese postmenopausal women, as well as samples from 21 postmenopausal women, who previously were obese but lost weight.
They found that obese women’s levels of free fatty acids were significantly higher.
However, blood levels of all the fatty acids fell significantly in women, who were obese at the outset of the study but later lost a significant amount of weight.
The findings were published in the journal Cancer Research, providing more information on how the specific metabolic pathways and genetic processes trigger Estrogen receptor-positive breast cancer.
To explore the impact that obesity has on ER-positive cancer cells, the researchers treated several lines of primary tumour and metastatic cancer cells with the blood of obese women.
They found that the cancer cells became more viable and multiplied, effects that increased as the fatty acid levels in the women’s blood samples increased.
ER-postive breast cancer is the most common type of breast cancer diagnosed today.
Exposure to the fatty acids in the women’s blood also appeared to make the disease more aggressive.
One line of primary tumour cells became more motile and an enzyme pathway that regulates cell growth, proliferation and survival in a metastatic cell line was activated.
The greater the cells’ level of exposure to the fatty acids, the more pronounced was the effect on this enzyme pathway, known as the mammalian target of rapamycin, or mTOR pathway.
Previous studies found that modifying the mTOR pathway’s interaction with ER-positive cells through a pathway-preferential estrogen compound elicited favourable responses in certain genes, such as preventing fat accumulation in mouse livers, without adversely affecting reproductive tissues.
To examine how this estrogen would affect gene expression in the current study, the researchers treated one group of breast cancer cells with oleic acid, a fatty acid, and another group of cells with a combination of oleic acid and the estrogen.
Among other effects, oleic acid increased the expression of genes involved in cell proliferation and downregulated about 500 genes, including those involved in fatty acid metabolism and adhesion with other cells.
However, these effects were greatly reduced in cells that were treated with the estrogen and oleic acid combination.
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