Research Papers:

Crosstalk between tongue carcinoma cells, extracellular vesicles, and immune cells in in vitro and in vivo models

Ahmed Al-Samadi _, Shady Adnan Awad, Katja Tuomainen, Yue Zhao, Abdelhakim Salem, Mataleena Parikka and Tuula Salo

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Oncotarget. 2017; 8:60123-60134. https://doi.org/10.18632/oncotarget.17768

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Ahmed Al-Samadi1, Shady Adnan Awad2,3,*, Katja Tuomainen1,4,*, Yue Zhao1, Abdelhakim Salem5, Mataleena Parikka6,7 and Tuula Salo1,8,9

1Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland

2Hematology Research Unit, Department of Hematology, University of Helsinki and Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland

3Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt

4Department of Otorhinolaryngology, Helsinki University Hospital, Helsinki, Finland

5Department of Internal Medicine, Clinicum, University of Helsinki, Helsinki, Finland

6Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

7Oral and Maxillofacial Unit, Tampere University Hospital, Tampere, Finland

8Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland

9Medical Research Center, Oulu University Hospital, Oulu, Finland

*These authors have contributed equally in this work

Correspondence to:

Ahmed Al-Samadi, email: [email protected]

Keywords: tongue cancer, immune cells, extracellular vesicles, in vitro model, cytotoxicity

Received: December 14, 2016    Accepted: April 19, 2017    Published: May 10, 2017


The crosstalk between immune cells, cancer cells, and extracellular vesicles (EVs) secreted by cancer cells remains poorly understood. We created three-dimensional (3D) cell culture models using human leiomyoma discs and Myogel to study the effects of immune cells on highly (HSC-3) and less (SCC-25) invasive oral tongue squamous cell carcinoma (OTSCC) cell lines. Additionally, we studied the effects of EVs isolated from these cell lines on the cytotoxicity of CD8+ T and NK cells isolated from three healthy donors. Our analysis included the effects of these EVs on innate immunity in zebrafish larvae. Activated immune cells significantly decreased the proliferation of both OTSCC cell lines and associated with a diminished invasion area of HSC-3 cells. In general, EVs from SCC-25 increased the cytotoxic activity of CD8+ T and NK cells more than those from HSC-3 cells. However, this effect varied depending on the source and the immune and cancer cell subgroups. In zebrafish, the amount of IL-13 mRNA was decreased by SCC-25 EVs. This study describes promising in vitro and in vivo models to investigate interactions between immune cells, cancer cells, and EVs.

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