Serum Exosomes Expressing CD9, CD63 and HER2 From Breast-Cancer Patients Decreased After Surgery of the Primary Tumor: A Potential Biomarker of Tumor Burden
Sachiko Inubushi, Tomonari Kunihisa, Marina KUNIYASU, SHOTARO INOUE, Mayuko Yamamoto, YUJI YAMASHITA, Mayuko Miki, Sachiko Mizumoto, Motoi Baba, Robert M. Hoffman, Hirokazu Tanino
Abstract
BACKGROUND/AIM: Exosomes are extracellular vesicles produced by both normal and cancer cells. Previous research has demonstrated that circulating exosomes derived from cancer cells may create a niche for future metastasis, distant from the primary tumor. In the present report, circulating exosomes were captured and quantified based on exosome-surface proteins in pre- and post-operative serum of breast cancer patients, focusing on the exosome markers CD9 and CD63, as well as HER2, a therapeutic target for breast cancer. MATERIALS AND METHODS: Eight breast cancer patients were recruited, and their pre- and post-operative serum samples were analyzed for CD63 and CD9; or CD9 and human epidermal growth factor receptor-2 (HER2), double-positive exosomes. An ExoCounter with antibody-conjugated beads was used to capture serum-derived exosomes. Sera from patients with tumors larger than 10 mm were used for analysis. The resected breast cancer was also histopathologically analyzed for the presence of HER2. RESULTS: CD63 and CD9 double-positive serum exosomes and CD9 and HER2 double-positive serum exosomes decreased after surgery in breast-cancer patients whose tumors expressed HER2, as determined by histopathological analysis. CONCLUSION: Serum exosomes expressing CD9, CD63 and HER2 are candidate biomarkers of tumor burden in HER2-positive breast-cancer patients.