Abstract A37: Self-seeding resulting from tumor-tumor IL-6 signaling protects lungs from osteosarcoma metastasis

Abstract

Abstract Metastatic osteosarcoma (OS) remains a fatal disease with overall survival less than 20%. The factors that drive metastasis remain poorly understood. Many have speculated on the biology that might drive development of metastasis after resection of a primary tumor. Our work suggests that OS tumors exhibit a high degree of self-seeding—“metastasis” of cancer cells back to the site of the primary tumor—and that circulating cells recolonize the primary tumor site preferentially over other sites. Removal of the primary tumor in orthotopic mouse models of OS triggers a redirection of circulating tumor cells toward colonization of alternative tissues, such as the lung. Mice that undergo amputation experience increased metastasis to the lungs relative to mice that continue to bear an orthotopic tumor. Our work demonstrates the involvement of IL-6 in the process of OS self-seeding. We show that osteosarcoma cells not only produce IL-6, but demonstrate directional migration and invasion in response to an IL6 gradient. Primary tumors engineered to lose the ability to produce IL6 demonstrate impairment of self-seeding and therefore become less able to “protect” from the development of lung metastasis. These results suggest that IL-6 is a primary mediator of tumor-tumor interactions that drive self-seeding in a process that might be amenable to therapeutic manipulation for the prevention of OS lung metastasis. Citation Format: Amanda J. Saraf, Helene Le Pommellet, Amy Gross, Sarah Winget, Ryan D. Roberts. Self-seeding resulting from tumor-tumor IL-6 signaling protects lungs from osteosarcoma metastasis [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr A37.