Systemic coagulopathy promotes host lethality in a new Drosophila tumor model

Malignant tumors trigger a complex network of inflammatory and wound repair responses, prompting Dvor-ak's characterization of tumors as wounds that never heal.1 Some of these responses lead to profound defects in blood clotting, such as disseminated intravascular coagulopathy (DIC), which correlate with poor prognoses.2-4 Here, we demonstrate that a new tumor model in Drosophila provokes phenotypes that resemble coagulopathies observed in patients. Fly ovarian tumors overproduce multiple secreted com-ponents of the clotting cascade and trigger hypercoagulation of fly blood (hemolymph). Hypercoagulation occurs shortly after tumor induction and is transient; it is followed by a hypocoagulative state that is defective in wound healing. Cellular clotting regulators accumulate on the tumor over time and are depleted from the body, suggesting that hypocoagulation is caused by exhaustion of host clotting components. We show that rescuing coagulopathy by depleting a tumor-produced clotting factor improves survival of tumor-bearing flies, despite the fact that flies have an open (non-vascular) circulatory system. As clinical studies suggest that lethality in patients with high serum levels of clotting components can be independent of thrombotic events,5,6 our work establishes a platform for identifying alternative mechanisms by which tumor-driven coagulopathy triggers early mortality. Moreover, it opens up exploration of other conserved mechanisms of host responses to chronic wounds.

Automated summary

Malignant tumors can cause complex inflammatory and wound repair responses, leading to defects in blood clotting. A new tumor model in Drosophila shows similarities to coagulopathies observed in patients. The tumor induces hypercoagulation followed by a defective wound healing state. By depleting a tumor-produced clotting factor, survival can be improved in tumor-bearing flies.