New discovery of how breast cancer spreads: What the finding could mean
Researchers know breast cancer is related to inflammation. Cornell University biomedical engineers devised a clever way to uncover what happens when cytokines that promote inflammation in the blood stream create a 'switch' that leads to breast cancer metastasis.
To find out how breast cancer cells spread through the blood and attach to cells, researchers in the lab of Michael R. King, professor of biomedical engineering at Cornell developed a flow chamber that mimics the lining of the blood vessels or endothelium.
Cancer cells spread by sticking to the endothelium. How they manage to adhere has been unclear.
For the study, researchers used hormone therapy-resistant breast cancer cells.
King and Yue Geng, graduate student in the field of biomedical engineering accidentally discovered the cancer cells interacted with receptor sites in blood vessels known as selectins. The process occurs in the same way as when white blood cells race to blood vessels to fight infection and inflammation.
Research has linked breast cancer to inflammation for a long time. The Cornell researchers found the cytokines IL-6 and TNF-alpha help malignant breast cancer cells stick to the endothelial wall and is the first step that leads to breast cancer spread.
The cytokines then help promote growth and clumping of breast cancer cells, triggering other cells to release more cytokines.
The researchers took their findings a step further by studying cultured cancer cells in human plasma with IL-6 and TNF. All of the cultured cancer cells showed the same metastatic behavior.
Finally, they tested how breast cancer spreads by looking at real life 3-dimensional tumor spheroids that they say are more physiologically accurate.
The tumors displayed the same type of interaction with the endothelium that was previously observed, but to an even greater extent.
When they treated the cells with the diabetes drug metformin that blocks IL-6, the cells weren’t able to metastasize, further confirming their findings.
The researchers say blocking breast cancer spread depends on undoing the switch that happens when cancer cells roll and stick to the endothelium. The finding could lead to new immunotherapies for breast cancer treatment that block inflammatory cytokines that start the whole process of breast cancer spread.
“Phenotypic Switch in Blood: Effects of Pro-Inflammatory Cytokines on Breast Cancer Cell Aggregation and Adhesion”
Yue Geng, et al.
January 23, 2013
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