Abstract
Angiogenesis is critical for cancer development and metastasis. Here we have employed a functional antibody library-based proteomic screen to identify proteins that participate in and might be used as therapeutic targets for tumor-related angiogenesis. Mice were immunized with human esophageal cancer endothelial cells (HECEC). The antibody library was established with the mouse spleen cells the serum of which had most anti-angiogenic effect. Monoclonal antibodies were subjected to an immunoreactive and functional screen and monoclonal antibodies that reacted strongly with cell surface antigens of HECECs and influenced their behavior were selected. Antigens that recognized by the antibodies were obtained by immunoprecipitation and then identified by mass spectrometry analysis. Migration-stimulating factor (MSF), the antigen of 1D2 antibody was identified using this approach. Further studies demonstrated that the 1D2 antibody suppressed MSF-effected migration and adhesion of HECECs on fibronectin matrix. Biodistribution assay showed that MSF targeting antibody 1D2 could specifically home to the xenograft with humanized blood vessel. Targeting treatment with 1D2 antibody significantly suppressed tumor growth through inhibition of human tumor-related angiogenesis. These results indicate that the functional antibody library-based proteomic screen can successfully identify proteins that involved in tumor-related angiogenesis and MSF may be a target for the anti-angiogenic treatment of the esophageal cancer.
Highlights
Angiogenesis is critical for cancer development and metastasis
By day 6, the human esophageal cancer endothelial cells (HECEC) formed netlike structures resembling a vascular network with the involvement of KYSE150 cells (Fig. 1A)
The co-cultured HECECs adopted a more extensive spindle-shaped morphology compared with monocultured HECECs with or without conditional medium
Summary
Angiogenesis is critical for cancer development and metastasis. Here we have employed a functional antibody library-based proteomic screen to identify proteins that participate in and might be used as therapeutic targets for tumor-related angiogenesis. Anti-angiogenic therapy is conceptually highly appealing for tumor treatment, few probes directing to the native endothelial cell surface proteins show validated tissue and function-specific pharmacodelivery in vivo [7,8,9]. Human esophageal cancer endothelium was isolated from carcinoma tissues, and their tumor-specific properties were maintained by co-culturing with tumor cells.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
