178 Oral - Models of Human Disease II
Saturday April 09, 11:30 AM - 11:45 AM

The Clot Thickens: Tumor-induced coagulopathy is a conserved driver of host mortality


Authors:
Katy Ong; Tsai-Ching Hsi; David Bilder

Affiliation: University of California, Berkeley, Berkeley, CA

Keywords:
h. tumorigenesis; h. hemocytes

Malignant tumors trigger a complex network of inflammatory and wound-healing responses, prompting Dvorak’s characterization of tumors as ‘wounds that never heal’. Some of these responses lead to profound clotting defects displayed by cancer patients, such as Disseminated Intravascular Coagulopathy (DIC), which correlate with poor prognoses. However, evidence suggests that lethality from coagulopathy is not fully explained by hemostatic dysregulation alone, raising the question of alternative mechanisms. Here, we demonstrate that tumor-induced coagulopathy is a paraneoplastic syndrome displayed by Drosophila as well as mammals. Fly tumors overproduce multiple components of the coagulation cascade, including the conserved Factor XIIIa homolog, and tumor-bearing flies exhibit abnormalities in clotting and wound healing that mirror DIC pathology. Critically, depleting coagulation components within the tumor significantly improved host survival, suggesting that coagulopathy is an unappreciated driver of mortality, even in insects that have an open circulatory system. We will discuss the underlying mechanism and the resulting insight into conserved responses of animals to malignancy.