Lung metastasis mysteries revealed

Researchers might be on to a new approach for preventing metastasis-prone lung cancer cells from spreading.

“We think that tumors have to learn how to metastasize because they can't do it initially. Cells change in response to cues from their external environment,” explained Jonathan Kurie, MD, a professor of thoracic/head and neck medical oncology at The University of Texas M. D. Anderson Cancer Center in Houston, Texas. Dr.Kurie's comments appeared in a statement issued by M. D. Anderson to announce the online publication of Dr. Kurie and colleagues' findings by The Journal of Clinical Investigation (www.jci.org/articles/view/42579/pdf). 

The discoveries revolve around two proteins. When one, known as Jagged2, binds externally to another, Notch—a membrane protein that protrudes through a surface of a cell—Jagged2 suppresses a microRNA (miR-200) that stops metastasis inside the cell.

Two Notch inhibitors are in clinical trial at M. D. Anderson. “These drugs might suppress the ability of primary tumors to metastasize,” said Dr. Kurie.

Although the drugs don't kill the primary tumor, they do keep the primary lung tumors “in jail,” according to Dr. Kurie. That is, the drugs block the tumor cells from transforming from immobile epithelial cells to a migratory cell that becomes part of an early event in metastasis.

The next step is to determine which of the four known Notch receptors suppress miR-200, consequently driving metastasis. The drugs currently under study are designed to inhibit an enzyme that activates all Notch receptors. Dr. Kurie suggested that drugs targeting specific Notch receptors might be more effective inhibitors of metastasis.

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