Abstract
Angiogenesis is essential for the development, growth, and metastasis of solid tumors. Vaccination with viable human umbilical vein endothelial cells (HUVECs) has been used for antitumor angiogenesis. However, the limited immune response induced by HUVECs hinders their clinical application. In the present study, we found that HUVECs induced by a tumor microenvironment using the supernatant of murine CT26 colorectal cancer cells exerted a better antiangiogenic effect than HUVECs themselves. The inhibitory effect on tumor growth in the induced HUVEC group was significantly better than that of the HUVEC group, and the induced HUVEC group showed a strong inhibition in CD31-positive microvessel density in the tumor tissues. Moreover, the level of anti-induced HUVEC membrane protein antibody in mouse serum was profoundly higher in the induced HUVEC group than in the HUVEC group. Based on this, the antitumor effect of a vaccine with a combination of induced HUVECs and dendritic cell-loading CT26 antigen (DC-CT26) was evaluated. Notably, the microvessel density of tumor specimens was significantly lower in the combined vaccine group than in the control groups. Furthermore, the spleen index, the killing effect of cytotoxic T lymphocytes (CTLs), and the concentration of interferon-γ in the serum were enhanced in the combined vaccine group. Based on these results, the combined vaccine targeting both tumor angiogenesis and tumor cells may be an attractive and effective cancer immunotherapy strategy.
Highlights
Colorectal carcinoma (CRC) is one of the most common and deadly cancers worldwide, and its incidence is on the rise
As migration and invasion are essential for the formation of new blood vessels, wound healing and transwell assays were performed to examine the effects of the tumor microenvironment on the migration and invasion abilities of human umbilical vein endothelial cells (HUVECs)
Results showed that the migration and invasion abilities were enhanced in the induced HUVEC group, and the expression levels of TEM1 and TEM8 were increased in the induced HUVEC group, which revealed that induced HUVECs had characteristics more like tumor vascular endothelial cells than HUVECs (Figure 1)
Summary
Colorectal carcinoma (CRC) is one of the most common and deadly cancers worldwide, and its incidence is on the rise. Tumor angiogenesis is required for cancer growth and metastasis and has been considered a potential target for CRC treatment [2]. Most antiangiogenic drugs, such as synthetic molecules and monoclonal antibodies, have obvious side effects and readily produce. Cells 2019, 8, 494 drug resistance, which limits their clinical application [3]. Immunotherapy of tumors with vaccines is another promising avenue of antiangiogenesis therapy to overcome these drawbacks [4,5,6]. Recent studies have demonstrated that a human umbilical vein endothelial cell (HUVEC) vaccine could inhibit tumors by initiating antiangiogenic effects with both cellular and humoral immunity [7,8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
