AEG-1 promotes angiogenesis and may be a novel treatment target for tongue squamous cell carcinoma

Oral Dis. 2020 Jul;26(5):876-884. doi: 10.1111/odi.13300. Epub 2020 Mar 10.

Abstract

Background: The study explored the potential function of astrocyte elevated gene-1 (AEG-1) on angiogenesis in tongue squamous cell carcinoma (TSCC) in TSCC cell lines.

Methods: The different degrees of angiogenesis were detected in TSCC cell lines expressing different levels of AEG-1 by chick chorioallantoic membrane (CAM) experimental model. Next, we established xenografts of different TSCC cell lines with different expression levels of AEG-1 in nude mice and conducted immunohistochemistry to evaluate the expression of the angiogenesis-associated factor, that is, vascular endothelial growth receptor factor 2 (VEGFR-2) and microvessel density (MVD). Vascular endothelial growth factor (VEGF) was detected by ELISA.

Results: CAM assay showed that the number of vessels was significantly reduced in AEG-1-down um1 cell line (p < .05), whereas the number was significantly increased in AEG-1-over um2 cell line (p < .05). Moreover, up-regulated AEG-1 expression level was associated with higher tumor angiogenesis, which was reflected by augmented expression levels of VEGF (p < .01), VEGFR-2 (p < .05), and MVD counting (p < .01).

Conclusions: This study demonstrated that AEG-1 can promote tumor angiogenesis in TSCC and inhibition of tumor angiogenesis by repressing the expression of AEG-1 may be a novel potential treatment approach for TSCC.

Keywords: Tongue squamous cell carcinoma; angiogenesis; astrocyte elevated gene-1; microvessel density; vascular endothelial growth receptor factor 2.

MeSH terms

  • Animals
  • Astrocytes
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / genetics
  • Cell Adhesion Molecules / genetics
  • Cell Line, Tumor
  • Head and Neck Neoplasms*
  • Heterografts
  • Humans
  • Membrane Proteins* / physiology
  • Mice
  • Mice, Nude
  • Prognosis
  • RNA-Binding Proteins* / physiology
  • Tongue Neoplasms* / drug therapy
  • Tongue Neoplasms* / genetics
  • Vascular Endothelial Growth Factor A

Substances

  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • RNA-Binding Proteins
  • Vascular Endothelial Growth Factor A