Editors' ChoiceCancer

Sleepy Time for Tumor Cells

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Science Translational Medicine  15 Aug 2012:
Vol. 4, Issue 147, pp. 147ec146
DOI: 10.1126/scitranslmed.3004722

We know that general anesthetics can stop pretty much anyone in their tracks—but what about cancer cells? For a cancer to metastasize, tumor cells must first break through the network of fibers and polysaccharides that provides structural support for healthy cells—the extracellular matrix. This process can be triggered by surgical manipulation, in part because of the tissue damage resulting from slowed blood flow followed by reperfusion. Conversely, general anesthesia during surgery has recently been shown to positively influence cancer outcomes; however, how anesthetics attenuate tumor growth remains unknown. Now, Müller-Edenborn and colleagues demonstrate that the inhaled anesthetics sevoflurane and desflurane impair the release and activity of matrix metalloproteinase-9 (MMP-9), which plays an important role in degradation of the extracellular matrix and subsequent tumor invasion.

The investigators cultured human neutrophils, the richest source of MMP-9 in the body, in the presence of interleukin-8 (IL-8), a proinflammatory cytokine that is released during reperfusion. Control neutrophils produced MMP-9 when exposed to IL-8; however, clinically relevant concentrations of sevoflurane or desflurane inhibited MMP-9 production. This difference was not related to neutrophil viability but was mediated through the IL-8 receptor. The same anesthetics also limited migration of human neutrophils through Matrigel, an experimental gel that simulates the extracellular matrix. Importantly, anesthetic treatment also limited migration of mouse colon cancer cells in the presence of neutrophils.

The findings of Müller-Edenborn et al. prompt further translational research into whether anesthetic technique during tumor operations can have a direct influence on cancer recurrence by modulating matrix-degrading activity that is triggered by surgery and required for invasiveness. Of course, the study is limited by the in vitro methodology and the use of murine cancer cells. However, if this finding is further validated in humans, perhaps we may yet be able to “put tumors to sleep,” at least long enough to successfully remove them from patients without the risk of further metastasis.

B. Müller-Edenborn et al., Volatile anesthetics reduce invasion of colorectal cancer cells through down-regulation of matrix metalloproteinase-9. Anesthesiology 117, 293–301 (2012). [PubMed]

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