Molecular Cause of Breast Cancer Metastasis Discovered

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Disrupt TGF-beta signaling, or ANGPTL4 expression, and lung metastasis is disrupted, the researchers found. Enhance that signaling, and lung metastasis is increased.

"This is a molecular and biological explanation of why and how responding to TGF-beta contributes to lung metastasis," concluded Massague.

This study also suggests anticancer therapies based on both TGF-beta (which are currently in development) and ANGPTL4 could be useful against metastatic breast cancer, he added.

According to Saxe, the observation that cancers have a way to select targets to spread to is not surprising. "Something like this had to be going on," he said. "But what is very nice and satisfying is to find a very clear mechanism like this to explain why some kinds of breast cell tumors metastasize to the bone and some to lung."

Massague said the reason ANGPTL4 helps cells colonize the lungs but not the bone has to do with the different architecture of the two tissues. Lung tissue is highly vascularized, yet capillaries present a relatively impenetrable barrier to metastasizing cells. Bone, on the other hand, is different, Massague explained, because it has windows and "...every day in the bone marrow, the capillaries have to let cells in and out."

Similar molecular discriminators may turn out to play a role in a variety of tumors, Saxe said. TGF-beta signaling in general, and ANGPTL4 in particular, may control metastasis in a variety of tumor types. Other signaling pathways could also be involved, and Saxe said he expects this study will spark new research to investigate those possibilities.

As Dr. Kornelia Polyak, a researcher with the Breast Cancer Genetics Lab at the Dana-Farber Cancer Institute at Harvard Medical School, pointed out, metastasis likely involves "an orchestra of genes that together can contribute to different steps" of the process. "It's likely to be a combination of genes, and this particular one [ANGPTL4] is one of them."

More information

For more on breast cancer, visit the National Cancer Institute.