Editors' ChoiceCancer

An Expanded Tumor Playing Field

See allHide authors and affiliations

Science Translational Medicine  27 Oct 2010:
Vol. 2, Issue 55, pp. 55ec165
DOI: 10.1126/scitranslmed.3001824

Bystanders are not just seen at sporting events but also make an appearance in tumor biology. The bystander effect (sometimes called the field effect) describes the benign cells near a tumor that harbor DNA damage similar to that seen in the tumor itself. Tumors have been implicated in this bystander effect, but the distance over which the bystander effect extends its influence has remained unclear. Now, Redon et al. report that tumors may trigger DNA damage in benign tissues that are far away from the site of the tumor and that an inflammatory cytokine called CCL2 may mediate this effect.

The authors first implanted melanoma, colon cancer, or sarcoma tumor cells subcutaneously into mice and then assessed the bystander effect in distant healthy tissues, such as the skin and gut. They found that in tumor-bearing mice, skin and gut tissue had more DNA double-strand breaks and DNA damage because of oxidative injury than did those tissues in control mice injected with saline. Furthermore, compared with control animals the tumor-bearing mice showed greater infiltration of not only their tumors but also their skin and gut tissue by macrophages, which are immune cells that mediate chronic inflammation. The investigators then discovered that the serum of tumor-bearing mice showed increases in a variety of cytokines, including CCL2, which is responsible for recruiting macrophages.

Next, the authors implanted the three different tumor types in mice that could not make CCL2 in order to test whether this cytokine was responsible for promoting the bystander effect in distant tissues. They saw no increase in DNA damage in the gut of the tumor-bearing mice that could not produce CCL2, suggesting that this cytokine mediates the bystander effect in distant tissues, presumably by boosting systemic chronic inflammation.

These new findings show that the bystander effect extends well beyond the immediate environment of the tumor and that the host immune system is required for this process. The next question is whether the bystander effect is present in cancer patients and, if so, how this information can be used to improve anticancer treatments.

C. E. Redon et al., Tumors induce complex DNA damage in distant proliferative tissues in vivo. Proc. Natl. Acad. Sci. U.S.A. 20 September 2010 (10.1073/pnas.1008260107). [Abstract]

Navigate This Article