Confocal laser-scanning microscopy shows how wound healing influences cancer

An international team of researchers used a microscopy technique to study the larvae of zebrafish to reveal how wound healing leads to skin cancer. Live imaging showed that neutrophils (the protective inflammatory cells of the body’s immune system) diverted from an induced wound to any nearby precancerous skin cells. The newly arrived neutrophils caused rapid division of these skin cells, which may cause them to progress to melanoma.

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"Our results provide direct visual evidence of a physical link between wound-associated inflammation and the development of skin cancer," says European Molecular Biology Organization (EMBO) member Paul Martin, a professor at Bristol University and the University of Cardiff. “White blood cells, in particular neutrophils, that typically serve as part of the body’s built-in immune system are usurped by nearby precancerous skin cells in a way that leads to the proliferation of tumor cells in our zebrafish model experimental system of human melanoma.”

The researchers used genetically modified larvae of zebrafish to watch the relationship between wound-associated inflammation and melanoma as the cancer took hold in the living fish. The cellular events and changes were observed with a special confocal laser-scanning microscope.

In further experiments, the researchers were also able to show that a specific type of signaling molecule released by neutrophils, prostaglandin E2, is part of the signal that drives the splurge of cell growth linked to the cancer in their experimental system. High levels of neutrophils were also detected in human clinical samples of melanomas that had been obtained from individuals whose cancers had open ulcers. Importantly, neutrophils were linked to increased proliferation of melanoma cells and poor survival, which suggests that these findings in fish may have considerable relevance to cancer patients.

The authors note that the findings of the study may have implications for cancer surgery. Minimally invasive surgery is beneficial to cancer patients in many situations and often the preferred treatment. However, particularly in cases where all cancerous tissue cannot be removed, the inflammatory response might influence the remaining cancer cells in the body. “Our studies to date suggest that several strategies might improve outcomes for patients including the possible use of therapeutics to dampen damage-induced inflammatory responses,” adds Martin.

Further work is in progress to better understand the relationship between the inflammatory response and skin cancer in the zebrafish model system. Studies are also needed to investigate what therapeutic or other strategies might bring better interventions for patients who have adverse tissue inflammation due to planned (biopsy or surgery) or unplanned (ulceration) tissue damage.

Full details of the work appear in The EMBO Journal; for more information, please visit http://emboj.embopress.org/content/early/2015/06/30/embj.201490147.

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