Exosome-Associated MTA1 in Circulation Is Elevated During Breast Cancer Progression.

Metastasis-associated protein 1 (MTA1) is overexpressed in breast cancer cells, and the MTA1 expression level is correlated with the metastasis and progression of breast cancer. We recently reported that MTA1 is transferred via exosomes from breast cancer cells to adjacent cells and to the circulation of breast cancer patients. However, whether exosome-associated MTA1 may serve as an indicator of breast cancer progression remains unknown. Wild-type MDA-MB-231 cells, MDA-MB-231 cells with MTA1 knockout, and human stromal cells were used to confirm MTA1 transfer via exosomes. Plasma was collected from nude mice (n = 6) implanted with MDA-MB-231 cells or MTA1-knockout MDA-MB-231 cells. Serum from patients with breast cancer (n = 59) and age- and sex-matched healthy subjects was collected. Exosomes from the plasma/serum were isolated via double filtration followed by the polymer precipitation method. Western blotting and ELISA were performed to detect MTA1. Knockout of MTA1 in MDA-MB-231 cells significantly reduced the tumor volume in nude mice. ELISA analysis of mouse plasma exosomes revealed that the level of exosome-associated MTA1 was significantly greater in mice implanted with wild-type MDA-MB-231 cells than in mice without implantation, and was reversed in mice implanted with MDA-MB-231 MTA1-knockout cells. The MTA1 level in serum-derived exosomes was significantly elevated in breast cancer patients compared to the matched healthy subjects. Detailed analysis revealed that exosome-associated MTA1 levels were significantly elevated in patients with stage III and IV breast cancer and in those with ER/PR-positive and Her2-positive tumors. ROC curve analysis revealed that serum exosome-associated MTA1 levels were highly accurate in predicting late-stage breast cancer.