Exosomal TACSTD2 promotes invasion, metastasis and glycolysis in ovarian cancer

Tumour-derived exosomes are involved in various cancer processes, including invasion, metastasis, and tumour microenvironment (TME) remodelling. However, the function and mechanism of exosomes in ovarian cancer (OC) are still under investigation. The present study investigated the effects of tumour-derived exosomes on the carcinogenesis and progression of OC.

OC gene expression profiles were obtained from The Cancer Genome Atlas (TCGA) database and two independent Gene Expression Omnibus (GEO) datasets (GSE7463 and GSE12470). The exosome related genes were obtained by intersecting with OC related exosomes in the ExoCarta database, subsequently, the exosome genes of interst were identified through performing survival analysis in the GEPIA database.The expression of genes selected were validated in OC cell lines (SKOV3, OVCAR3 and A2780) and ascites of OC patients through western blot and PCR. And further knockdown and overexpression of this gene were performed in OC cells to detect their effects on cell proliferation, migration, and invasion. Subsequently, the potential biological functions and regulatory mechanisms were explored based on the Gene Set Enrichment Analysis (GSEA), and changes in relevant target proteins were validated through western blot. Furthermore, SKOV3-luc + cells were injected intraperitoneally into female BALB/c nude mice to construct an in orthotopic xenograft mouse model, in order to evaluate the effect of differential genes on in vivo OC.

Based on the results of bioinformatics analysis, TACSTD2 was selected for experimental validation. Cell function experiments verified that exosomal TACSTD2 promoted proliferation and metastasis by mediating glycolysis in OC. Animal experiments indicated that exosomal TACSTD2 promoted abdominal metastasis in OC. The in vitro and in vivo experimental results were consistent with the bioinformatics analysis.

TACSTD2, which can be detected in ovarian cancer-derived exosomes, plays an important role in the invasion, migration and glycolysis in ovarian cancer. Furthermore, we have discovered that TACSTD2 may promote the progression of ovarian cancer by regulating glycolysis. Further research will enable its potentially prognostic marker and therapeutic target for ovarian cancer.