Endostatin inhibits lymph node metastasis by a down-regulation of the vascular endothelial growth factor C expression...

Area of Science:

• Oncology
• Molecular Biology
• Biotechnology

Background:

• Anti-angiogenic therapy is a promising strategy for treating malignant tumors.
• Endostatin is known to inhibit tumor growth and metastasis via the vascular system.
• The role of endostatin in lymph node metastasis is not well-established.

Purpose of the Study:

• To investigate the effect of endostatin on lymph node metastasis.
• To explore the potential of endostatin gene therapy in inhibiting cancer spread.

Main Methods:

• Recombinant adenovirus expressing endostatin (Ad-end) was constructed.
• In vitro assays assessed endothelial cell proliferation and tube formation.
• In vivo studies utilized human oral squamous cell carcinoma xenografts in nude mice (subcutaneous and orthotopic models).
• Analysis included CD31 and 5'-nase staining for vascular and lymphatic vessels, and RT-PCR and Western blot for VEGF-C expression.

Main Results:

• Ad-end inhibited endothelial cell proliferation and tube formation in vitro.
• Ad-end suppressed tumor growth in both subcutaneous and orthotopic oral cancer models.
• Ad-end significantly reduced lymph node metastasis in the orthotopic model.
• Tumors treated with Ad-end showed reduced blood and lymphatic vessel density.
• Vascular Endothelial Growth Factor C (VEGF-C) expression was downregulated in Ad-end-treated tumor cells.

Conclusions:

• Endostatin gene therapy (Ad-end) effectively inhibits tumor growth and metastasis.
• Endostatin suppresses lymphangiogenesis and lymph node metastasis, potentially by downregulating VEGF-C.
• This study highlights endostatin as a potential therapeutic agent against lymph node metastasis in oral cancer.