Abstract 4488: Osteosarcoma cells interact with bronchial cells in lung to drive production of pro-metastatic 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, further stimulate tumor cell production of IL6 and CXCL8 in a feed-forward mechanism. Co-culture experiments have 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 show that these interactions result from exchange of soluble mediators secreted by each cell type. Proteomic profiling of bronchial cell supernatants following incubation with OS conditioned media identified a number of intriguing candidate mediators, which might facilitate the growth and survival of OS cells within the microenviroment of the lung. Some of those same candidate mediators trigger expression of IL6 and CXCL8 in OS cell cultures. These results suggest a paracrine loop mechanism, where OS cells trigger a response from lung stromal cells that promotes survival and proliferation of the OS cells, establishing a favorable niche for the development of metastasis. Citation Format: John M. Hinckley, Amy Gross, Ryan Roberts. Osteosarcoma cells interact with bronchial cells in lung to drive production of pro-metastatic cytokines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4488.