Abstract
Tumor angiogenesis is a hallmark of cancer and is involved in the tumorigenesis of solid tumors. B7-H3, an immune checkpoint molecule, plays critical roles in proliferation, metastasis and tumorigenesis in diverse tumors; however, little is known about the biological functions and molecular mechanism underlying B7-H3 in regulating colorectal cancer (CRC) angiogenesis. In this study, we first demonstrated that the expression of B7-H3 was significantly upregulated and was positively associated with platelet endothelial cell adhesion molecule-1 (CD31) level in tissue samples from patients with CRC. In addition, a series of in vitro and in vivo experiments showed that conditioned medium from B7-H3 knockdown CRC cells significantly inhibited the migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs), whereas overexpression of B7-H3 had the opposite effect. Furthermore, B7-H3 promoted tumor angiogenesis by upregulating VEGFA expression. Recombinant VEGFA abolished the inhibitory effects of conditioned medium from shB7-H3 CRC cells on HUVEC angiogenesis, while VEGFA siRNA or a VEGFA-neutralizing antibody reversed the effects of conditioned medium from B7-H3-overexpressing CRC cells on HUVEC angiogenesis. Moreover, we verified that B7-H3 upregulated VEGFA expression and angiogenesis by activating the NF-κB pathway. Collectively, our findings identify the B7-H3/NF-κB/VEGFA axis in promoting CRC angiogenesis, which serves as a promising approach for CRC treatment.
Highlights
Colorectal cancer (CRC) is the third most prevalent cancer worldwide, as well as the third leading cause of cancer-related deaths[1]
Our results showed that the level of B7-H3 was much higher in colorectal cancer (CRC) tissue samples as compared with normal tissues
Zhang et al found that immunoglobulin-like transcript 4 (ILT4) drove B7-H3 expression via PI3K/ AKT/mTOR signaling in non-small cell lung cancer[39]
Summary
Colorectal cancer (CRC) is the third most prevalent cancer worldwide, as well as the third leading cause of cancer-related deaths[1]. With the development of therapeutic methods such as surgical resection, radiotherapy, chemotherapy, immunotherapy, and targeted therapy, the 5-year survival rate of patients with CRC has been significantly improved in recent years[2,3,4]. Disease metastasis and relapse are still challenges for CRC clinical therapy[5]. It is urgent that we understand the molecular pathogenesis of CRC and identify novel therapeutic targets for CRC treatment. As a hallmark of cancer, angiogenesis is a critical step in the tumorigenesis of solid cancers[6].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
