Abstract 5849: Exosomes promote survival and migration in squamous head and neck cancer cells after ionizing radiation: Evidence for a bystander effect

Abstract

Abstract Exosomes are important intercellular communicators in the acute radiation stress-response. Here we show that exosomes from head and neck tumor cells confer protective signals to their neighboring cells. This promotes the tumorigenic and radioresistant phenotype of head and neck cancer cells. Isolation of exosomes was performed by serial ultracentrifugation of conditioned medium collected from irradiated or non-irradiated head and neck cancer cell lines BHY and FaDu. Quantification by NanoSight technology indicated an increased exosome release from irradiated compared to non-irradiated cells 24 hours after treatment. To test whether the released exosomes influence the radiation response, exosomes isolated from non-irradiated and irradiated donor cells were transferred on non-irradiated and irradiated recipient cells. We found an enhanced uptake of exosomes, when transferred to irradiated recipient cells compared to the transfer to non-irradiated cells. Functional analyses indicate increased survival of irradiated recipient cells after exosome transfer. These findings mesh with increased DNA double strand break repair that we found after the transfer of exosomes isolated from irradiated cells. Moreover we observed an increased migration and enhanced chemotaxis induced motility after the transfer of exosomes isolated from irradiated cells. To investigate whether differential protein loading into exosomes is responsible for the functional differences we performed proteome analysis of the exosomes. We have identified 679 proteins, of which 39 were up- and 36 were downregulated by irradiation of the donor cells. In a good agreement with our functional assays, the proteome profiling showed that exosomal proteins were mainly involved in wound healing. Exosomes are functional components of the response of tumor cells to therapeutic radiation exposure. In a clinical context these results suggests that radiotherapy modified exosomes may influence the cancer progression, metastasis and therapeutic success. Citation Format: Lisa Mutschelknaus, Omid Azimzadeh, Theresa Heider, Klaudia Winkler, Marcus Vetter, Soile Tapio, Juliane Merl-Pham, Rosemarie Kell, Stephan Huber, Lena Edalat, Vanja Radulovic, Natasa Anastasov, Carsten Peters, Michael John Atkinson, Simone Moertl. Exosomes promote survival and migration in squamous head and neck cancer cells after ionizing radiation: Evidence for a bystander effect [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 5849. doi:10.1158/1538-7445.AM2017-5849