Newly Identified Metabolites Connect Colon Cancer to Thrombosis

Patients with cancer are at 4-to-7-fold higher risk of venous thromboembolism (VTE). The risk of cancer-associated VTE varies with the type of cancer, underscoring the presence of cancer type-specific drivers and a need for appropriate animal models, both of which have been understudied. Here, we generated a colon cancer-specific mouse model and probed for the development of VTE and factors that might induce it. To this end, a group of athymic animals injected with human colon adenocarcinoma cell line (HT-29) underwent inferior vena cava (IVC) ligation, a validated model of venous thrombosis. Compared to corresponding controls (age- and gender-matched), mice on regular chow diet with xenografts exhibited significantly higher IVC clot weights. Plasma analysis of metabolites led us to identify the tryptophan metabolites, Kynurenine and Indoxyl Sulfate, which are known activator of the Aryl Hydrocarbon Receptor (AHR), as significantly elevated in the cancer model (2-3 fold; p Disclosures No relevant conflicts of interest to declare.