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; Tuula Salo

doi:10.18632/oncotarget.17768

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

Oncotarget. 2017 May 10;8(36):60123-60134. doi: 10.18632/oncotarget.17768. eCollection 2017 Sep 1.

Authors

Ahmed Al-Samadi¹, Shady Adnan Awad^#^{2

3}, Katja Tuomainen^#^{1

4}, Yue Zhao¹, Abdelhakim Salem⁵, Mataleena Parikka^{6

7}, Tuula Salo^{1

8

9}

Affiliations

¹ Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.
² Hematology Research Unit, Department of Hematology, University of Helsinki and Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland.
³ Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
⁴ Department of Otorhinolaryngology, Helsinki University Hospital, Helsinki, Finland.
⁵ Department of Internal Medicine, Clinicum, University of Helsinki, Helsinki, Finland.
⁶ Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
⁷ Oral and Maxillofacial Unit, Tampere University Hospital, Tampere, Finland.
⁸ Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.
⁹ Medical Research Center, Oulu University Hospital, Oulu, Finland.

^# Contributed equally.

Abstract

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.

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