Antibody library-based tumor endothelial cells surface proteomic functional screen reveals migration-stimulating...

Area of Science:

• Oncology
• Immunology
• Proteomics

Background:

• Tumor angiogenesis is crucial for cancer progression and metastasis.
• Identifying novel therapeutic targets for tumor angiogenesis remains a significant challenge in cancer treatment.

Purpose of the Study:

• To identify proteins involved in tumor-related angiogenesis using a functional antibody library-based proteomic screen.
• To evaluate the therapeutic potential of targeting identified proteins for esophageal cancer treatment.

Main Methods:

• Immunization of mice with human esophageal cancer endothelial cells (HECEC) and establishment of a functional antibody library.
• Screening of monoclonal antibodies for reactivity with HECEC surface antigens and functional effects on cell behavior.
• Identification of target antigens via immunoprecipitation and mass spectrometry, including Migration-stimulating factor (MSF).
• In vitro and in vivo validation of the MSF-targeting 1D2 antibody's efficacy in suppressing angiogenesis and tumor growth.

Main Results:

• The 1D2 antibody specifically recognized and targeted Migration-stimulating factor (MSF).
• The 1D2 antibody inhibited MSF-mediated migration and adhesion of HECECs.
• Biodistribution assays confirmed specific homing of the 1D2 antibody to humanized blood vessels in xenografts.
• Targeted treatment with the 1D2 antibody significantly suppressed tumor growth by inhibiting angiogenesis.

Conclusions:

• A functional antibody library-based proteomic screen is effective for identifying proteins involved in tumor angiogenesis.
• Migration-stimulating factor (MSF) is a promising therapeutic target for anti-angiogenic treatment of esophageal cancer.
• The 1D2 antibody demonstrates potential as a targeted therapy for esophageal cancer by inhibiting angiogenesis.