title: Endothelial cell Bcl-2 and lymph node metastasis in patients with oral squamous cell carcinoma.
abstract: BACKGROUND
  Loco-regional spread of disease causes high morbidity and is associated with the poor prognosis of malignant oral tumors. Better understanding of mechanisms underlying the establishment of lymph node metastasis is necessary for the development of more effective therapies for patients with oral cancer. The aims of this work were to evaluate a possible correlation between endothelial cell Bcl-2 and lymph node metastasis in patients with oral squamous cell carcinoma (OSCC), and to study signaling pathways that regulate Bcl-2 expression in lymphatic endothelial cells.
  
  
  METHODS
  Endothelial cells were selectively retrieved from paraffin-embedded tissue sections of primary human OSCC from patients with or without lymph node metastasis by laser capture microdissection. RT-PCR was used to evaluate Bcl-2 expression in tumor-associated endothelial cells and in tumor cells. In vitro, mechanistic studies were performed to examine the effect of vascular endothelial growth factor (VEGF)-C on the expression of Bcl-2 in primary human lymphatic endothelial cells.
  
  
  RESULTS
  We observed that Bcl-2 expression is upregulated in the endothelial cells of human oral tumors with lymph node metastasis as compared to endothelial cells from stage-matched tumors without metastasis. VEGF-C induced Bcl-2 expression in lymphatic endothelial cells via VEGFR-3 and PI3k/Akt signaling. Notably, OSCC cells express VEGF-C and induce Bcl-2 in lymphatic endothelial cells.
  
  
  CONCLUSIONS
  Collectively, this work unveiled a mechanism for the induction of Bcl-2 in lymphatic endothelial cells and suggested that endothelial cell Bcl-2 contributes to lymph node metastasis in patients with oral squamous cell carcinoma.
authors.affiliation: Department of Oral Pathology, Federal University of Pelotas, Pelotas, RS, Brazil.
authors.forename: Sandra B C
authors.initials: SB
authors.lastname: Tarquinio
authors.forename: Zhaocheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Neiva
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Polverini
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Nör
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000556:secondary*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D004729:Endothelium, Lymphatic / Q000187:drug effects / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000473:pathology*; D051058:Oncogene Protein v-akt / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology; D042582:Vascular Endothelial Growth Factor C / Q000494:pharmacology; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one