ISSN: 0034-8376
eISSN: 2564-8896






An Epidermal Growth Factor Motif of Developmental Endothelial Locus 1 Protein Inhibits Efficient Angiogenesis in Explanted Squamous Cell Carcinoma In Vivo



Hisataka Kitano, Divisions of Oral Surgery, Nihon University School of Medicine, Tokyo, Japan
Atsushi Mamiya, Divisions of Oral Surgery, Nihon University School of Medicine, Tokyo, Japan
Tomomi Ishikawa, Divisions of Oral Surgery, Nihon University School of Medicine, Tokyo, Japan
Yusuke Fujiwara, Divisions of Oral Surgery, Nihon University School of Medicine, Tokyo, Japan
Yoh Masaoka, Divisions of Physiology, Nihon University School of Medicine, Tokyo, Japan
Toshio Miki, Divisions of Physiology, Nihon University School of Medicine, Tokyo, Japan
Chiaki Hidai, Medical Education Center, Nihon University School of Medicine, Tokyo, Japan


Background: Cancer gene therapy using a nonviral vector is expected to be repeatable, safe, and inexpensive, and to have longterm effectiveness. Gene therapy using the E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has been shown to improve prognosis in a mouse transplanted tumor model. Objective: In this study, we examined how this treatment affects angiogenesis in mouse transplanted tumors. Materials and methods: Mouse transplanted tumors (SCCKN human squamous carcinoma cell line) were injected locally with a nonviral plasmid vector encoding E3C1 weekly. Histochemical analysis of the transplanted tumors was then performed to assess the effects of E3C1 on prognosis. Results: All mice in the control group had died or reached an endpoint within 39 days. In contrast, one of ten mice in the E3C1 group had died by day 39, and eight of ten had died or reached an endpoint by day 120 (p < 0.01). Enhanced apoptosis in tumor stroma was seen on histochemical analyses, as was inhibited tumor angiogenesis in E3C1-treated mice. In addition, western blot analysis showed decreases in active Notch and HEY1 proteins. Conclusion: These findings indicate that cancer gene therapy using a nonviral vector encoding E3C1 significantly improved life-span by inhibiting tumor angiogenesis.



Keywords: Cancer Gene Therapy. Developmental Endothelial Locus-1. Tumor Angiogenesis. Tumor Stroma.