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

Authors

  • Sandra B. C. Tarquinio,

    1. Department of Oral Pathology, Federal University of Pelotas, Pelotas, RS, Brazil
    2. Angiogenesis Research Laboratory, Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry
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  • Zhaocheng Zhang,

    1. Angiogenesis Research Laboratory, Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry
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  • Kathleen G. Neiva,

    1. Angiogenesis Research Laboratory, Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry
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  • Peter J. Polverini,

    1. Department of Periodontics and Oral Medicine
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  • Jacques E. Nör

    1. Angiogenesis Research Laboratory, Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry
    2. Department of Biomedical Engineering, University of Michigan College of Engineering
    3. Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, MI, USA
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Jacques E. Nör, DDS, MS, PhD, Dentistry, Otolaryngology, and Biomedical Engineering, University of Michigan, 1011 N. University Rm. 2309, Ann Arbor, MI 48109-1078, USA. Tel: 734 936 9300, Fax: 734 936 1597, E-mail: jenor@umich.edu

Abstract

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.

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