Abstract 5209: Ionizing radiation abrogates pro-tumorigenic effects from cancer-associated fibroblasts in xenografts

Non-malignant elements of tumors play fundamental roles in both cancer sustainability and responses to therapies. In the context of clinical radiotherapy (RT), all cells that reside in the tumor mass receive radiation, but the impact of cancer-associated fibroblasts (CAFs) to treatment outcomes remains largely unexplored. In this study, we have investigated the effects of radiation on the natural pro-tumorigenic actions of CAFs in animals. Ionizing radiation (IR) was delivered to CAFs either as a single-high dose or fractionated medium doses. Tumor development was compared in xenografts after co-implantation of A549 lung tumor cells with irradiated or non-irradiated human lung CAFs. Quantitative histology and immunohistochemistry was applied to investigate potential biological mechanisms behind tumor growth regulations. As expected, CAFs showed resistance to radiation-induced cell death, however, the enhanced tumorigenic effects observed with admixed non-irradiated CAFs was nullified. Quantitative determinations of parameters such as desmoplasia, angiogenesis, inflammation, innate immunity or tumor cell proliferation revealed enhanced blood vessel density in tumors established with irradiated CAFs. Experiments to ascertain fate of implanted CAFs showed that both irradiated and non-irradiated CAFs only reside at the implantation site during early stages, suggesting that the regulatory functions of admixed CAFs may take place during the initial phases of tumor formation. In this study, we show that CAFs receiving ionizing radiation lose their pro-tumorigenic potential in vivo, affecting angiogenesis and possibly other mechanisms related to tumor engraftment. This finding represent a previously unknown advantageous effect induced by radiotherapy, which adds to the well-known direct cytotoxic effects on transformed epithelial cells. Note: This abstract was not presented at the meeting. Citation Format: Turid Hellevik, Maria T. Grinde, Jorg Vik, Ketil A. Camilio, Inigo Martinez-Zubiaurre. Ionizing radiation abrogates pro-tumorigenic effects from cancer-associated fibroblasts in xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5209. doi:10.1158/1538-7445.AM2017-5209