Single chain precursor prohaptoglobin promotes angiogenesis by upregulating expression of vascular endothelial growth factor (VEGF) and VEGF receptor2

• Prohaptoglobin, precursor haptoglobin, is a novel angiogenic factor.
• Prohaptoglobin promotes angiogenesis via VEGF/VEGFR2 signalling.
• Prohaptoglobin is present in sera of patients with liver cancer.
• Prohaptoglobin may be a potential biomarker for cancer.

Prohaptoglobin (proHp) is processed into mature haptoglobin via site-specific cleavage. Although haptoglobin has been well studied, the functions of proHp remain unclear. We investigated the angiogenic action of proHp in endothelial cells, demonstrating that proHp upregulated vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) expression and endothelial sprouting and branching. ProHp-induced sprouting was attenuated by a VEGFR2 inhibitor. Moreover, proHp was detected in sera of cancer patients by immunoprecipitation and Western blot. These findings indicate that proHp promotes angiogenesis via VEGF/VEGFR2 signalling, and serum proHp level may be a useful biomarker for diseases associated with angiogenesis.