NSMASE2 EXPRESSION IN ASCITES FLUIDS, PRIMARY AND METASTATIC TUMORS OF OVARIAN CARCINOMA

Esther Channah Broner 1 Claes Göran Trope 3,4 Ben Davidson 2,3 Reuven Reich 1
1Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem
2Division of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo
3The Medical Faculty, University of Oslo, Oslo
4Norwegian Radium Hospital, Oslo University Hospital, Department of Gynecologic Oncology, Oslo

Background:

Ovarian cancer is the leading cause of death from gynecological cancers in western countries. The disease is asymptomatic in the early stages, and is usually diagnosed at an advance stage. Primary solid tumors, solid metastases, and effusions to the peritoneal and pleural cavities characterize the tumor as it progresses.

Exosomes, naturally occurring biological nanovesicles, have been shown to contain lipids, proteins, and nucleic acid sequences. It has been implicated that this content might be considered as a “messenger system” that exhibits paracrine bioactivities and facilitate tumor communication within the local tumor microenvironment and distantly through transfer of regulatory messages to other cells. Although the precise mechanism of the release of exosomes has yet to be elucidated, several studies have indicated on nSmase2 in the release of exosomes.

Study Aims:

Our aim is to compare the level of expression of nSmase2 in the different sites of ovarian carcinoma and to seek a correlation between nSmase2 levels and different aspects of clinical outcomes and treatment regiments.

Methods:

Cells from ascites fluids, primary and metastatic tumors of over 100 ovarian carcinoma patients with different clinical outcomes and treatment regiments were analyzed by qPCR and western blot.

Results:

nSmase2 mRNA is elevated in effusions vs. primary and metastatic tumors and elevated expression correlates with poor survival in ovarian carcinoma patients. Surprisingly, in the same samples, nSmase2 protein is reduced in effusions vs. primary and metastatic tumors. This discrepancy may be explained by the probable extra cellular existence of nSmase2 protein both in effusion fluids and exosomes.

Conclusion:

To the best of our knowledge, this study is the first to correlate between levels of nSmase2 and poor survival in ovarian carcinoma patients. Hopefully, a fuller understanding of the exosomes secretion process will lead to the development of a therapy for this disease.








 




Powered by Eventact EMS