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Signals found that recruit host animals' cells, enabling breast cancer metastasis
Date:5/22/2014

mong breast cancer cells, menenchymal stem cells and white blood cells. One positive feedback loop brought mesenchymal stem cells close in to the breast cancer cells. A separate loop of signals between the stem cells and cancer cells caused the cancer cells to release a chemical "beacon" that drew in white blood cells. The concentrations of all the signals in the web were increased by the presence of HIF-1 and ultimately, by low-oxygen conditions.

The team then used genetic engineering to reduce the levels of the cell-recruiting signals in breast cancer cells and implanted those cells into female mice. Compared with unaltered breast cancer cells, those with reduced recruiting power grew into similar-sized tumors, Semenza says, but were much less likely to spread.

All of the breast cancer cells used in the study were so-called triple-negative, meaning they lack receptors for estrogen, progesterone and human epidermal growth factor receptor 2, so they do not respond to therapies that target those receptors. In people, triple-negative breast cancers also tend to be more deadly than other breast cancers because they contain more HIF-1, Semenza says. "This study adds to the evidence that a HIF-1 inhibitor drug could be an effective addition to chemotherapy regimens, especially for triple-negative breast cancers," he says. Several potential drugs of this kind are now in the early stages of development, he notes.


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Contact: Shawna Williams
shawna@jhmi.edu
410-955-8236
Johns Hopkins Medicine
Source:Eurekalert

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