Exosomes as Modulators of Tumor Microenvironment

The metastatic process involves the manipulation of the tumor microenvironment to optimize the conditions for local growth and to enable dissemination of the tumor cells through out the patient’s body.

Recent studies point to the exosomes, small (30-100 nm) vesicles secreted continuously by both, normal and diseased cells, as important components of tumor microenvironment involved in intercellular communication. Exosome cargo reflects the molecular and cellular content of the cell of origin such as growth factors, receptors, proteases, coding and non-coding RNA and certain lipids. They also reflect dynamic changes in the cellular compartments that are occurring in health and at different stages of a disease.

Ovarian cancer (OC) is the most lethal and second most common gynecological malignancy in the western world. Current knowledge of the biological factors that drive OC metastasis as solid lesions or effusions is incomplete at best. In the present study we analyzed the expression profile of miRNAs in exosomes isolated from the effusion fluid of OC patients and compared them to the cellular profile of miRNAs in those patients. Our results indicated on specific miRNA population that correlated with the survival of the patients. Further, the same population of miRNAs increased the invasive potential of OC cells in vitro and in vivo models.

Examination of the secretory mechanism of exosomes revealed the expression of nSMmase2, Tsap6 and Rab27a mRNA in our tumor samples. Clinical analysis shows that elevated nSmase2 and Tsap6 mRNA expression correlates with poor survival (p<0.036) and less favorable response to chemotherapy, respectively (p<0.027).

Understanding the precise mechanism of exosome secretions and analysis of their cargo opens a new avenue for potential treatment of this yet incurable disease.