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.