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AACR: Genomics and the Progression of Cancer Metastasis

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At the annual meeting of the American Association for Cancer Research in Chicago this week, one panel discussion focused on how genomics is helping cancer researchers figure out how cancer spreads. Harvard's Raghu Kalluri focused his talk on the stromal factors that determine the rate of a cancer's metastasis. For metastasis to take place, the tumor stroma — the 75 percent to 95 percent of a tumor's cells that act as the functional, supportive framework of a tumor but are not cancerous — need to be involved, Kalluri said. By manipulating the stroma, a doctor could significantly affect the rate of metastasis in a patient. "When you look at a human tumor, it's important to appreciate that the bulk of it is stroma, not cancer cells," Kalluri added. "It's assumed that everything that’s present in a tumor is bad. The assumption is that all constituents of a tumor are aiding the cancer to grow and metastasize — but recent research has shown this to not be true."

In particular, Kalluri said, the pericytes — which usually surround endothelial cells — are an important component of the tumor stroma, when it comes to metastasis. It's already been noted that pericyte loss is associated with invasive breast cancer, and that pericyte coverage of endothelial cells changes as cancer progresses — the more invasive a cancer is, the less pericyte coverage there is. Kalluri's team conducted a study which showed an association between low pericyte coverage and low disease-free and overall survival. This suggests, Kalluri said, that pericytes may be negative regulators of metastasis. Another study from his lab showed that ablation of pericytes leads to impaired tumor growth, but more metastasis. Further, ablation leads to more circulating cancer cells, as pericyte coverage of endothelial cells is lost — ablation leads to "leaky vessels" and more permeability, Kalluri added. He suggested that one possible strategy to reduce metastasis would be to ablate pericytes to reduce the size of a tumor, and, in addition, treat patients with a Met inhibitor to reduce the chances of metastasis.

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