Expression and characterization of bifunctional fusion proteins possessing antitumor and thrombolytic function for...

Area of Science:

• Biotechnology
• Oncology
• Biochemistry

Background:

• Cancer patients frequently develop thrombosis, a condition lacking effective treatments.
• Existing therapies for tumor-related thrombosis are insufficient.
• Staphylococcal enterotoxin C2 (SEC2) and Sak possess antitumor and thrombolytic activities, respectively.

Purpose of the Study:

• To construct and evaluate novel fusion proteins for targeted cancer therapy.
• To combine the antitumor activity of SEC2 with the thrombolytic activity of Sak.
• To enhance tumor specificity using octreotide, a tumor-targeting peptide.

Main Methods:

• Engineered fusion proteins (ΔSEC2-ΔSak and ΔSak-ΔSEC2) incorporating octreotide.
• Expressed and purified fusion proteins.
• Assessed fusion protein bioactivities, including lymphocyte proliferation, tumor cell growth inhibition (BGC-823), and thrombolysis.
• Confirmed tumor-binding capacity via coimmunoprecipitation with SST receptor 2 antibody.

Main Results:

• Fusion proteins retained the bioactivities of both SEC2 and Sak.
• Fusion proteins demonstrated significant inhibition of human gastric carcinoma BGC-823 growth.
• Fusion proteins exhibited thrombolytic activity.
• Coimmunoprecipitation confirmed that fusion proteins specifically bind to somatostatin (SST) receptor 2 on tumor surfaces.

Conclusions:

• The developed fusion proteins possess dual antitumor and thrombolytic functions.
• Octreotide conjugation enables specific targeting of fusion proteins to tumor cells.
• These fusion proteins represent a promising strategy for targeted therapy of cancer-associated thrombosis.