Editors' ChoiceCancer

Casting Infection as Cancer’s Best Friend

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Science Translational Medicine  14 Aug 2013:
Vol. 5, Issue 198, pp. 198ec137
DOI: 10.1126/scitranslmed.3007269

Cancer patients, whose immune function is suppressed by both the cancer itself and by chemotherapy, are known to be at high risk for serious infections and require aggressive treatment with antibiotics in order to prevent sepsis and death. Now, Yan and colleagues provide evidence that not only are infections in the setting of cancer directly harmful, but they may also worsen the underlying cancer.

In mouse models of pneumonia induced by Escherichia coli or simulated by means of lipopolysaccharide (LPS) injection, the authors observed increased uptake of intravenously injected cancer cells into the lungs as well as an increase in lung metastasis from mouse breast tumors. In agreement with the in vivo results, bronchoalveolar lavage fluid from mice that received LPS or E. coli promoted the migration of tumor cells in culture. Additional in vitro experiments showed that the migration-stimulating effect of LPS depends on chemokine receptor CXCR4 and one of its ligands, extracellular ubiquitin, and could be blocked by AMD3100, an inhibitor of CXCR4. Last, the authors demonstrated that treating the E. coli lung infection with amoxicillin, a commonly used antibiotic, greatly decreased the uptake of intravascular tumor cells into the lungs.

The results of this study suggest yet another rationale for aggressively treating infections in cancer patients and also shed light on the mechanisms involved in the interplay between infection and cancer. Future studies will need to confirm these findings in additional models of metastasis and to determine whether the same phenomenon can be observed in humans. In the meantime, we can continue to intensively treat infections in cancer patients, now with the knowledge that we may also be helping the patients fight the underlying disease.

L. Yan et al., The ubiquitin–CXCR4 axis plays an important role in acute lung infection–enhanced lung tumor metastasis. Clin.Cancer Res., published online 6 August 2013 (10.1158/1078-0432.CCR-13-0011). [Abstract]

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