MIT researchers have discovered proteins involved in cancer metastasis

About 90 percent of cancer deaths are caused by tumors that have spread from their original locations. This process, known as metastasis, requires cancer cells to break loose from their neighbors and from the supportive scaffold that gives tissues their structure.

MIT cancer biologists have now discovered that certain proteins in this structure, known as the extracellular matrix, help cancer cells make their escape. The researchers identified dozens of proteins that surround highly metastatic tumors, but not less aggressive tumors, and found that four of those proteins are critical to metastasis.

The findings could lead to new tests that predict which tumors are most likely to metastasize, and may also help to identify new therapeutic targets for metastatic tumors, which are extremely difficult to treat.

“The problem is, all the current drugs are targeted to primary tumors. Once a metastasis appears, in many cases, there’s nothing you can do about it,” says Richard Hynes, leader of the research team and a member of MIT’s Koch Institute for Integrative Cancer Research. “In principle, one could imagine interfering with some of these extracellular proteins and blocking metastasis in a patient. We’re a long way from that, but it’s not inconceivable.”

In this study, the researchers focused on about 1,000 proteins, including about 300 that have been identified in genomic studies as components of the matrix. The remaining proteins include enzymes that modify or degrade the matrix and growth factors that bind to it.

To compare the extracellular matrix proteins found in different tumor types, the researchers implanted metastatic and nonmetastatic human breast cancer cells into mice. They identified 118 extracellular matrix proteins that were found in both types of tumors. However, there were also several dozen proteins that were abundant in either metastatic or nonmetastatic tumors, but not both.

The researchers also compared their results with human tumor samples and found that when the proteins they had identified in mice were overexpressed in human tumors, the patients had lower survival rates. It would be impractical to do this kind of large-scale protein screen in patients, but it could be possible to test samples for certain proteins using antibodies, say the researchers, who are now developing such antibodies.

“That could become part of a kit that doctors would use to distinguish a patient who has a tumor that’s going to metastasize, so they would follow the patient differently from a patient with a tumor they know won’t metastasize,” Naba says.

The researchers are now seeking extracellular matrix proteins that are overexpressed in other metastatic cancers, including colon and pancreatic cancers. They are also studying whether extracellular matrix proteins in tissues to which escaped tumor cells often metastasize — such as the bone, liver, and lungs — make them more receptive to invading cancer cells. If such proteins could be identified, they could also be good drug targets.

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