Tumor cells have developed various mechanisms in defense against applied treatment, which prevent their total elimination from an organism. One of the underestimated mechanisms of defense is secretion of highly specialized double-membrane structures called exosomes. They play a crucial role in the control of the local microenvironment and intracellular communication. It has been shown that the exosomes can be carriers of various proteins, lipids, miRNAs and mRNAs. There are extensive data concerning the influence and participation by exosomes in metastasis and cancer progression. It has been demonstrated that exosomes are involved in multidrug resistance mechanisms, radiation-induced bystander effect and epithelial-mesenchymal transition. Furthermore, exosomes are able to form a premetastatic niche and enable the escape of cancer cells from recognition by host immune cells. Moreover, exosomes are responsible for the formation of vessels. This indicates the significance of secreted extracellular vesicles in the development and prognosis of cancer. The aim of the present review is to briefly describe the role of exosomes in tumor biology.

Background: In patients with Ovarian Cancer (OvCa) exosomes released by tumor cells are present in the plasma and could be involved in tumor progression. This study examines the association between the exosome presence/protein content in plasma of OvCa patients and disease outcome, response to standard therapy and/or tumorresistance to therapies in patients studied at diagnosis and also serially during and after therapy. Design and methods: Exosomes were purified from OvCa patients’ plasma (n=22), patients with benign tumors (n=10) or (n=10) healthy controls (NC) using ultracentrifugation. Exosomes were visualized by scanning electron microscopy. Their protein content was measured. The presence of MAGE 3/6 and TGF-β1 in exosomes was evaluated in Western blots. Results: The OvCa patients’ plasma contained higher levels of exosomal proteins (p<0.05) compared to those isolated from plasma of patients with benign tumors or NC. Exosomes isolated from OvCa patients’s plasma carried TGF-β1 and MAGE3/6, which distinguished OvCa patients from those with benign tumors and NC. High protein levels of exosomes were seen in newly diagnosed patients; however in advanced stages of OvCa patients the protein content of isolated exosomes was significantly higher than that of early stages. The exosome levels variably changed during/after chemotherapy, and correlations between the changes in exosomal protein levels and clinical data suggested that the protein content of exosomes might be useful in predicting responses to therapy and prognosis in OvCa patients. Conclusion: Analysis of plasma exosomes levels offers a novel approach to diagnosis and monitoring response to therapies in OvCa patients.

Fucoidans have been reported to exert anticancer effects with simultaneous low toxicity against healthy tissue. That correlation was observed in several cancer models, however, it has never been investigated in head and neck cancer before. To magnify the efficacy of conventional therapy, the administration of agents like fucoidan could be beneficial. The aim of this study was to evaluate the anticancer effect of Fucus vesiculosus (FV) extract alone and with co-administration of cisplatin in head and neck squamous cell carcinoma (HNSCC) in vitro. MTT assay results revealed an FV-induced inhibition of proliferation in all tested cell lines (H103, FaDu, KB). Flow cytometric cell cycle analysis showed an FV-induced, dose-dependent arrest in either S/G2 phase (H103, FaDu) or G1 arrest (KB). Furthermore, a dose-dependent gain in apoptotic fraction was observed. Western blot analysis confirmed the induction of apoptosis. A significant dose-dependent increase in reactive oxygen species (ROS) production was revealed in the H103 cell line, while FaDu cells remained unresponsive. On the contrary, an HPV-positive cell line, KB, demonstrated a dose-dependent decrease in ROS synthesis. Moreover, fucoidan enhanced the response to cisplatin (synergistic effect) in all cell lines with the HPV-positive one (KB) being the most sensitive. These results have been confirmed by flow-cytometric apoptosis analysis. In conclusion, we confirmed that fucoidan exhibits anticancer properties against HNSCC, which are manifested by the induction of apoptosis, regulation of ROS production, cell cycle arrest, and inhibition of proliferation.