Abstract B39: Osteosarcoma cells interact with bronchial cells in lung to drive production of prometastatic cytokines

Abstract

Abstract The survival rate for patients diagnosed with osteosarcoma (OS) drops from 70% to an abysmal 20% when diagnosed with lung metastasis. We have shown that metastatic colonization of lungs by OS cells depends on the production of IL6 and CXCL8 by tumor cells, which seems to increase within the metastatic niche of the lung. Identification of key tumor-host interactions that drive this phenomenon will facilitate the development of novel therapies aimed at prevention of metastases in patients diagnosed with OS. We hypothesized that OS cells interact with lung tissues in ways that establish paracrine signal amplification loops, where IL6 and CXCL8 stimulate lung-resident cells to produce secondary signaling molecules that, in turn, stimulate tumor cell production of IL6 and CXCL8 in a feed-forward mechanism. Coculture experiments identified strong interactions between OS cells and primary cultures of bronchial epithelial cells and lung smooth muscle cells. Exposure of OS cells to conditioned supernatants from the primary cell cultures and vice versa showed that these interactions result from exchange of soluble mediators secreted by each cell type. Proteomic profiling of the resultant supernatants identifies a number of interesting candidate mediators, which might also affect the growth and survival of OS cells within the microenviroment of the lung. These results suggest a mechanism for the establishment of a metastatic niche favorable to OS cells within lung tissues. Citation Format: John Hinckley, Amy Gross, Ryan Roberts. Osteosarcoma cells interact with bronchial cells in lung to drive production of prometastatic cytokines [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 B39.