Exosomal B7-H3 facilitates colorectal cancer angiogenesis and metastasis through AKT1/mTOR/VEGFA pathway

B7-H3 (CD276), an immune checkpoint molecule, is aberrantly overexpressed in many types of cancer, and plays important roles in tumor immune evasion, carcinogenesis and metastasis, as well as angiogenesis . However, the mechanisms underlying B7-H3-promoted angiogenesis are still largely unknown. In this study, based on the observation of overexpression of B7-H3 on the tumor cells and vascular endothelial cells (VECs) in colorectal cancer (CRC) tissues, we investigated the roles of cancer cell-drived exosomal B7-H3 in tumor angiogenesis and metastasis through crosstalk between cancer cells and VECs. We found that CRC cell-drived exosomal B7-H3 was uptaken by human umbilical vein endothelial cells (HUVECs) and consequently activated the AKT serine/threonine kinase 1 (AKT1) / mechanistic target of rapamycin kinase (mTOR) / vascular endothelial growth factor A (VEGFA) signaling pathway , thus augmenting the abilities of migration, invasion and tube formation of HUVECs. Furthermore, administration of CRC cell-drived exosomes with reinforced B7-H3 promoted the pulmonary angiogenesis and metastasis of CRC cells in mice. In addition, high expression of B7-H3 was observed in urinary exosomes isolated from CRC patients. Our findings reveal that CRC-derived exosomal B7-H3 promotes tumor angiogenesis and metastasis by activating the AKT1/mTOR/VEGFA signaling pathway. It provides novel insights into the roles of CRC-drived exosomes in CRC progression.