Canstatin

Mechanism of Action

• Binds integrins alphavbeta3 and alphavbeta5 on proliferating endothelial cells, blocking vitronectin-mediated adhesion and migration
• Inhibits PI3K/Akt and FAK phosphorylation downstream of integrin engagement, reducing endothelial survival signaling
• Induces endothelial apoptosis via FADD-dependent extrinsic caspase-8/3 pathway activation
• Simultaneously inhibits endothelial migration (via integrin blockade) and proliferation (via PI3K suppression) in complement to tumstatin effects
• Anti-angiogenic activity requires intact disulfide bonds in the NC1 domain; reduction abolishes activity

Research Findings

• Canstatin inhibited tumor growth and angiogenesis in breast, colon, and prostate xenograft mouse models at 10-30 mg/kg doses
• Canstatin plus paclitaxel showed synergistic anti-tumor effects in ovarian cancer mouse models
• Canstatin plasma levels reduced in patients with aggressive cancers; potential prognostic biomarker alongside tumstatin
• Canstatin expression in tumor endothelium inversely correlates with microvessel density and tumor grade
• Fragment analysis identified aa118-222 as the minimum anti-proliferative domain; aa1-117 mediates anti-migratory effects

Research Protocols

• Mouse tumor model: 0.5-30 mg/kg SC or IP daily or every 48h of recombinant canstatin protein
• In vitro: 10-1000 nM recombinant canstatin in endothelial tube formation or Boyden migration assays
• Combination with paclitaxel: canstatin 5-10 mg/kg + paclitaxel 5-10 mg/kg in xenograft models
• No approved clinical protocols; research-grade protein only

Interactions

• Tumstatin: complementary anti-angiogenic activity; distinct integrin binding domains allow additive combination
• Arresten (Col4a1 NC1): third collagen IV NC1 fragment; all three together cover broad anti-angiogenic spectrum
• Paclitaxel/taxanes: synergistic anti-tumor effects in preclinical models; canstatin sensitizes endothelium

Safety Profile

Investigational research protein. No human dosing data. Recombinant canstatin well tolerated in rodent studies at anti-tumor doses. No approved therapeutic product.

Legal & Regulatory

Research use only