Influence of buffy coat-derived putative endothelial progenitor cells on tumor growth and neovascularization in oral squamous cell carcinoma xenografts

Clin Oral Investig. 2019 Oct;23(10):3767-3775. doi: 10.1007/s00784-019-02806-2. Epub 2019 Jan 28.

Abstract

Objectives: The aim of this murine in vivo study was to investigate whether buffy coat-derived putative endothelial progenitor cells (BCEPC) alter tumor growth and neovascularization in oral squamous cell carcinomas (OSCC).

Materials and methods: A murine xenograft model using the PCI-13 oral cancer cell line was deployed of which n = 24 animals received 2 × 106 BCEPC by transfusion whereas the control group (n = 24) received NaCl (0.9%) instead. Tumor size, volume, and capillary density were determined by sonography and measurement with a caliper. Immunohistochemical analysis was carried out with antibodies specific for Cytokeratins, Flt-4, Podoplanin, and Vimentin.

Results: In the experimental group, systemic application of BCEPC significantly increased tumor volume to 362.49% (p = 0.0012) and weight to 352.38% (p = 0.0018) as well as vascular densities to 162.15% (p = 0.0021) compared with control tumors. In addition, BCEPC-treated xenografts exhibited higher Cytokeratin expression levels by a factor of 1.47 (p = 0.0417), Podoplanin by a factor of 3.3 (p = 0.0020) and Vimentin by a factor of 2.5 (p = 0.0001), respectively.

Conclusions: Immunohistochemical investigations support the notion that BCEPC transfusion influences neovascularization and lymphatic vessel density, thereby possibly promoting tumor progression. Future studies, which will include gene expression analysis, should help to define the possible role of BCEPC during OSCC progression in more detail.

Clinical relevance: Endothelial progenitor cells (EPCs) could serve as a target structure for the treatment of OSCC and possibly other solid tumors.

Keywords: Endothelial progenitor cell; Lymphangiogenesis; Neovascularization; Oral cancer.

MeSH terms

  • Animals
  • Blood Buffy Coat
  • Carcinoma, Squamous Cell / pathology*
  • Endothelial Progenitor Cells / cytology*
  • Female
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, Nude
  • Mice, SCID
  • Mouth Neoplasms / pathology*
  • Neovascularization, Pathologic*
  • Transplantation, Heterologous