To date, over 2000 species of protein have been identified from OvCa-derived exosomes according to ExoCarta. Their involvement in tumour progression and metastasis has been reported in many of these identified proteins, including membrane proteins (Alix, TSG 101), and tetraspanins (CD24, CD44, CD63, CD37, CD53, CD81), as well as enzymes (phosphate isomerase, peroxiredoxin, gelatinolytic enzymes, aldehyde reductase). Moreover, a study by Liang et al. illustrated that OvCa-derived exosome proteins were highly enriched in signal pathways associated with carcinogenesis. They found that a subset of proteins overexpressed in ovarian cancer tissue were present in the exosomal protein list, including epithelial cell surface antigen (EpCAM), proliferation cell nuclear antigen (PCNA), tubulin beta-3 chain (TUBB3), epidermal growth factor receptor (EGFR), apolipoprotein E (APOE), claudin 3 (CLDN3), fatty acid synthase (FASN), ERBB2, and L1CAM (CD171). These protein may also be a source of diagnostic markers and targets for therapeutic methods for Ovca [
22]. Among them, EpCAM has been extensively studied and, is used as a biomarker or prognostic factor of many cancers. For example, Huang et al. demonstrated an intricate relationship between EpCAM-regulated transcription and altered biophysical properties of cells that promote EMT in advanced endometrial cancer [
23]. However, there are drawbacks to the use of EpCAM as an OVCA biomarker. For example, Shen’s group compared the characteristics of exosomes derived from human ovarian epithelial cells (HOSEPiC) and three OvCa cell lines (OVCAR3, IGROV1, and ES-2), and found that the labeled rates by anti-EpCAM antibodies were 16.4, 23.7, 15.7, and 18.5%, respectively suggesting that EpCAM may not be an appropriate marker for detecting early stages of OvCa [
24]. The negative outcome may have been due to the fact that EpCAM can be cleaved from exosomes via serum metalloproteinase [
25]. While some articles suggest an outlet for combining EpCAM with CD24 to detect Ovca-derived circulation exosomes, large scale clinical trials is needed to verify this hypothesis. In terms of the protein CLDN3, Morin’s group found that CLDN3 was not likely to represent a useful biomarker compared to CLDN4, which had a sensitivity of 51% (32/63) and specificity of 98% (49/50) for the detection of OvCa [
26].
Early detection of the resistance to platinum-based therapy is critical for improving the treatment of Ovca. Increased expression of annexin A3 is a mechanism for platinum resistance in ovarian cancer, which is associated with exocytosis and the release of exosomes [
28]. For therapy potential, the exosomal ADAM15 ectodomain effectively inhibits cancer progression by blocking the integrin-mediated MEK/ERK signalling pathway, providing insight into the functional significance of exosomes that generate tumor-inhibitory factors [
29].