Dendritic cells and vascular endothelial growth factor-C in human oral squamous cell carcinoma

Objective

Dendritic cells (DCs) are antigen-presenting cells that can activate naive T cells and thus play a role in tumor immunity. Vascular endothelial growth factors (VEGFs) produced and secreted by various cancers have been reported to inhibit DC differentiation from progenitor cells. However, the relationship between VEGF-C and DCs in oral squamous cell carcinoma (OSCC) remains unclear.

Methods

Formalin-fixed paraffin-embedded samples of 172 OSCCs were studied. Immunohistological staining was performed to determine the density of S100- and CD1a- positive DCs, D2–40-positive lymphatic vessels, and the grade of VEGF-C expression in OSCCs. OSCC cell lines were cultured and examined for VEGF-C secretion using ELISA.

Results

In comparison to pathological lymph node-negative (PN-) cases, the density of DCs in cancer tissues was significantly lower in PN-positive (PN+) cases, whereas the lymphatic vessel density of cancer tissues was significantly higher in PN+ cases. The density of DCs decreased significantly with increasing VEGF-C expression, indicating a weak inverse relationship. There was a strong positive correlation between VEGF-C expression and lymphatic vessel density. ELISA revealed VEGF-C secretion in various OSCC cell lines, particularly HSC-3, and this increased over time.

Conclusions

These results indicate that VEGF-C expressed by OSCC may increase lymphangiogenesis and create an environment that promotes lymph node metastasis.