Endothelial cell Bcl-2 and lymph node metastasis in patients with oral squamous cell carcinoma

• Published in: Journal of oral pathology & medicine 2012-02, Vol.41 (2), p.124-130
• Main Authors: Tarquinio, Sandra B. C., Zhang, Zhaocheng, Neiva, Kathleen G., Polverini, Peter J., Nör, Jacques E.
• Format: Article
• Language: English
• Subjects: angiogenesis; Biological and medical sciences; biomarkers; Biomarkers, Tumor - analysis; Blotting, Western; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - secondary; Cells, Cultured; Chromones - pharmacology; Dentistry; Endothelial Cells - drug effects; Endothelial Cells - pathology; Endothelium, Lymphatic - drug effects; Endothelium, Lymphatic - pathology; Enzyme Inhibitors - pharmacology; Female; head and neck cancer; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; lymphangiogenesis; Lymphatic Metastasis - pathology; Male; Medical sciences; Middle Aged; Morpholines - pharmacology; Mouth Neoplasms - pathology; Oncogene Protein v-akt - drug effects; oral cancer; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - drug effects; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - analysis; Proto-Oncogene Proteins c-bcl-2 - drug effects; Signal Transduction - physiology; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; vascular endothelial growth factor; Vascular Endothelial Growth Factor C - pharmacology; Vascular Endothelial Growth Factor Receptor-3 - drug effects
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/j.1600-0714.2011.01081.x

J Oral Pathol Med (2012) 41: 124–130 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.