Lightning Talk & Poster Australasian Extracellular Vesicles Conference 2018

Ovarian cancer cell invasiveness is associated with differential expression of proteins within exosomes which facilitate ovarian cancer tumor growth and metastasis in-vivo (#55)

Mona Alharbi 1 , Andrew Lai 1 , Dominic Guanzon 1 , Felipe Zuñiga 2 , Yaowu He 3 , Gregory E Rice 1 2 , John D Hooper 3 , Carlos Salomon 1 2 3 4
  1. Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane , QLD 4029, Australia.
  2. Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile
  3. Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia.
  4. Maternal-Fetal Medicine , Department of Obstetrics and Gynecology, Ochsner Clinic Foundation,, New Orleans , USA.

Exosomes can be selectively packed with a range of molecules that create a favorable microenvironment for cancer cells and facilitating metastasis. We aimed to explore the effect of exosomes on tumor growth/metastasis in a xenograft model and assess the changes in the proteomic content of tumor cells and exosomes from mice.

Exosomes were isolated from highly invasive SKOV-3 (exo-SKOV-3) and less invasive OVCAR-3 (exo-OVCAR-3) ovarian cancer cell lines. Exosomes (10ug/ml) were injected into a xenograft model, twice a week for six weeks and the tumor growth was monitored using IVIS imaging. Tissue and circulating exosomes obtained from the mice were subjected to SWATH MS/MS, followed by ingenuity pathway analysis (IPA) to determine canonical pathways and biofunctions associated with dysregulated proteins.

IVIS imaging indicated that the tumor burden in mice injected with exo-OVCAR-3 was higher than in mice injected with exo-SKOV-3 (p=0.004). However, mice injected with exo-SKOV-3 had more tumor nodules throughout the peritoneal cavity. Proteomic analysis of the cancer tissue obtained from mice injected with exo-SKOV-3 compared to exo-OVCAR-3 identified the differential expression (p<0.05) of 105 proteins, including S100A10, Calnexin, STIM1 and MRP1. Interestingly, the protein profile in tumor tissue obtained from mice injected with exo-SKOV-3 was associated with the Wnt canonical pathway (β-catenin). We also found 36 proteins with differential expression in exosomes from mice treated with exo-SKOV-3, including CRKL and SEPT9 (p<0.04).

 Our study suggests that exosomes derived from aggressive cancer cells are able to accelerate tumor metastasis, contributing to ovarian cancer progression by regulating Wnt canonical pathway.