Cells release a heterogeneous population of membrane enclosed vesicles termed extracellular vesicles (EVs) that play a role in intercellular communication. In the context of tumour-derived EVs as mediators of cancer development and progression, this heterogeneity could mean certain EV subpopulations fulfil unique roles in the biological processes underlying cancer biology. In the case of ovarian cancer, there is emerging evidence for the role of ovarian cancer-derived EVs in the distinct form of ovarian cancer metastasis called peritoneal dissemination. Here, we employed a two-step size exclusion chromatography approach to study heterogeneity of EVs released by ovarian cancer cells. EVs were isolated from cell culture supernatant using size exclusion chromatography (SEC). Subsequently, isolated EVs were fractionated into EV-subpopulations by high resolution size exclusion chromatography (HR-SEC).
We observed that only certain EV subpopulations support ovarian cancer cell adhesion. Cell adhesive EVs had different biophysical characteristics, a distinct proteome and a unique cell adhesion molecule fingerprint as compared to the non-adhesive EVs. Our findings highlight the complex role of EVs in cancer progression and development. A better understanding of the unique EV components contributing to ovarian cancer adhesion could result in the discovery of new targets for the treatment of ovarian cancer. Furthermore, dissecting EV heterogeneity will allow for more detailed study of EV biology and will facilitate biomarker discovery as well as highly specific engineering of EV-based therapeutics.