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Discovery Could Mean a New Target for Stopping Metastasis

What causes metastasis? What turns a tumor from a localized phenomena to a widespread disease? At Wistar, many of our scientists study the genetic changes that promote this dangerous turn of events. This March, in the journal Cancer Research, Wistar's Frank Rauscher, III, Ph.D., published findings on nature of a simple signaling protein that may help drive the metastatic spread of cancer.

The protein, LIMD2, correlates with bladder, melanoma, breast, and thyroid tumors that have become metastatic. Wistar scientists have also developed and patented a monoclonal antibody that may one day be used as a prognostic test to see if tumors have LIMD2, and plans are underway to create inhibitors—potential drugs that may target cells that produce the protein. 

"This is the result of a five year effort to characterize LIMD2, which is a new protein that we found to be expressed only in metastatic lesions, and not in the primary tumor or in normal tissues or organs,” said Rauscher, a professor in The Wistar Institute Cancer Center. “LIMD2 is a great candidate for targeting with a drug, which would inhibit the ability of these cells to leave a primary tumor and to colonize other organs.”  

According to Rauscher, LIMD2 is part of a family of proteins that communicate signals to the cell nucleus from the cytoskeleton of the cell—the structural scaffolding that supports the cell. Scientists have looked to these proteins as potential drivers of metastasis, since they control signals that regulate how the cell interacts with nearby cells. One such area that researchers have explored is how cells may migrate and adhere to other tissues, which are traits tumors use to metastasize. LIMD2, in particular, is a key component to a chain of chemical events that control cell motility, or movement, which is a defining characteristic of metastasis, Rauscher says. 

“Cancer metastasis is really the final frontier in cancer medicine, because metastasis kills,” Rauscher said. “We can treat a primary tumor, usually successfully, with surgery, drugs, chemotherapy or radiation, but once the cancer spreads to organs throughout the body it frequently becomes unstoppable.”

“We contend that LIMD2 is a marker that could help physicians profile tumors, and a potential drug target that could yield a potent therapy for a variety of advanced cancers, perhaps in combination with existing or emerging therapies,” Rauscher said.