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Systemic coagulopathy promotes host lethality in a new Drosophila model

ABSTRACT: Malignant tumors trigger a complex network of inflammatory and wound repair responses, prompting Dvorak's characterization of tumors as 'wounds that never heal'. Some of these responses lead to profound defects in blood clotting, such as Disseminated Intravascular Coagulopathy (DIC), which correlate with poor prognoses. Here, we demonstrate that a new tumor model in Drosophila provokes phenotypes that recapitulate coagulopathies observed in patients. Fly ovarian tumors overproduce multiple secreted components 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 such that tumor-bearing flies are defective in wound healing. Hypocoagulation is associated with exhaustion of host clotting components from the body, which is dependent on a tumor-produced clotting factor. Interestingly, clinical studies suggest that lethality in patients with high serum levels of clotting components can be independent of thrombotic events. We show that depleting tumor-produced clotting factors improves survival of tumor-bearing flies, despite the fact that flies have an open circulatory system. Our work establishes a platform for identifying alternative mechanisms by which tumor-driven coagulopathy triggers early mortality, as well as exploring other conserved mechanisms of host responses to chronic wounds.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE207849 | GEO | 2023/06/23

REPOSITORIES: GEO

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