Asian Scientist (Aug. 16, 2013) – Cancer metastasis requires tumor cells to acquire properties that allow them to escape from the primary tumor site, travel to a distant place in the body, and form secondary tumors.
But first, an advance team of molecules produced by the primary tumor sets off a series of events that create a network of nurturing blood vessels for arriving primary tumor cells to set up shop.
In lung cancer, the formation of that niche likely involves immune cells and moderate levels of VEGF and other molecules that promote the formation of new blood vessels, or angiogenesis. But little is known about how the local lining, or endothelial, cells are activated at the niche.
Now, researchers in Japan and the United States have discovered that the signaling protein calcineurin upregulates another molecule, Ang-2 that promotes angiogenesis.
In their study, published in Cell Reports, the researchers found that hyperactivation of calcineurin in genetically altered mice led to increased lung metastases. Inhibition of calcineurin or Ang-2, however, blocked metastases in lung cells of the mice.
The findings may provide insights into common cancer metastasis patterns, such as the tendency of prostate cancer to spread to the bones, or melanoma to the brain.
Because calcineurin acts on the pathways that set up sites of metastasis away from the primary tumor sites, it could be a potential target for future cancer therapies; however it is also active in the immune system.
In fact, calcineurin is inhibited by cyclosporine, which is used to combat transplant rejection, so using these types of drugs would be tricky for cancer unless they can be targeted specifically towards endothelial cells.
The researchers will now investigate whether calcineurin is important for metastases in other organs or whether this pathway is specific for lung metastases.
The article can be found at: Minami et al. (2013) The Calcineurin-NFAT-Angiopoietin-2 Signaling Axis In Lung Endothelium Is Critical For The Establishment Of Lung Metastases.
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Source: University of Pennsylvania School of Medicine; Photo: snre/Flickr/CC.
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