Stressors alter intercellular communication and exosome profile of nasopharyngeal carcinoma cells.
BACKGROUND
Head and neck cancers comprise the sixth most common cancer type worldwide. One of the most remarkable malignancies of the head and neck is the cancer of the nasopharynx, with a strong metastatic tendency already in the early stage. Besides the conventional pathways of metastasis formation, the information content of exosomes produced by the cancer cells may play a key role in metastatic transformation. The aim of this study was to investigate how stressors alter the characteristic of tumor derived exosomes.


METHODS
In our experimental model, we compared the quantity and content of exosomes produced by a nasopharyngeal carcinoma cell line (5-8F) under conventional (chemotherapy) and alternative (Ag-TiO2-catalyzed reactive oxygen species generation) cytostatic treatment. After isolation, exosomes were identified by atomic force microscopy and quantified with Nanosight NS500 device. MicroRNA content of them was analyzed using SOLiD 5500xl technology. The sequences were annotated in CLC Genomics Workbench version 5.5.1.


RESULTS
Beyond the classic chemotherapeutic agent (doxorubicin), Ag-TiO2in a photo-catalytic process also showed cytostatic activity. Tumor cell damage induced by the cytostatic treatments significantly altered the number of released exosomes and led to the predominance of tumor suppressors in the exosomal miRNA profile.


CONCLUSIONS
Our results suggest that the intercellular communication between tumor cells and surrounding stroma cells can be altered by microenvironment which increased quantity of exosomes and diversity of miRNAs in this study. Imbalance of oncogenic and tumor suppressor miRNAs caused by cytostatic treatments may influence the antiproliferative and metastasis inhibitory effect of cytostatic agents.
Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
Maria
M
Harmati
Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Szeged, Hungary.
Zsofia
Z
Tarnai
Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Szeged, Hungary.
Gabor
G
Decsi
Department of Traumatology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Sandor
S
Kormondi
Biological Application of the Atomic Force Microscope Research Group, Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
Zsolt
Z
Szegletes
Department of Physical Chemistry and Materials Sciences, University of Szeged, Szeged, Hungary.
Laszlo
L
Janovak
MTA-SZTE Supramolecular and Nanostructured Materials Research Group, University of Szeged, Szeged, Hungary.
Imre
I
Dekany
Molecular Neuro-Oncology Research Unit, Medical University of Vienna, Vienna, Austria.
Okay
O
Saydam
Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
Edina
E
Gyukity-Sebestyen
Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
Gabriella
G
Dobra
Sequencing Platform, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
Istvan
I
Nagy
Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Szeged, Hungary.
Katalin
K
Nagy
Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.|Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Szeged, Hungary.
Krisztina
K
Buzas
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002450:Cell Communication; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment
D000903:Antibiotics, Antineoplastic; D054697:Cytostatic Agents; D035683:MicroRNAs; D004317:Doxorubicin
cytostatic agents; exosomes; microRNAs; nanoparticles; nasopharyngeal carcinoma