Simultaneous expression of furin and vascular endothelial growth factor in human oral tongue squamous cell carcinoma progression

被引:64
作者
de Cicco, RL
Watson, JC
Bassi, DE
Litwin, S
Klein-Szanto, AJ [1 ]
机构
[1] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA
[2] Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA
[3] Fox Chase Canc Ctr, Dept Biomath & Biostat, Philadelphia, PA 19111 USA
关键词
D O I
10.1158/1078-0432.CCR-03-0670
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Squamous cell carcinoma (SCC) of the tongue is a common malignancy of the oral cavity. Furin convertase activates several precursor matrix metalloproteinases; involved in the degradation of the extracellular matrix. The pattern of expression of furin and vascular endothelial growth factor-C (VEGF-C), two key molecules in neoplasm development, was examined during the progression from normal epithelium to invasive SCC. Experimental Design: We evaluated furin and VEGF-C expression and microvessel density (MVD) by immunohistochemistry in human tongue sections harboring normal epithelium, dysplastic epithelium, and/or SCC. Sections from 46 glossectomy specimens were assessed for furin expression. A selected group of 15 cases, each containing normal epithelium, precursor lesions, and invasive SCC, were further studied for furin and VEGF-C expression and MVD quantification. We also evaluated the pattern of furin expression and VEGF-C processing by Western blot analysis in three SCC cell lines with different degrees of aggressiveness. Results: Furin and VEGF-C expression was notably higher in most precursor lesions and SCCs than in normal epithelia. Approximately 60% (n = 26) and 100% (n = 15) of the normal epithelia showed low-intensity staining for furin and VEGF-C, respectively. Intense staining for furin and VEGF-C was detected in -80% (n = 34) and 100% (n = 15) of the SCCs, respectively. A significant correlation was seen between the expression of these two markers (Spearman's test, P < 0.00002). We found a statistically significant increase in MVD when either dysplasia (432 +/- 19.06; P < 0.05) or SCC (546 +/- 17.24) was compared with normal epithelium (315 +/- 17.27; P < 0.0001). SCC71, the most aggressive cell line analyzed, was the one with the highest furin expression. This cell line totally processed the VEGF-C proform, whereas the less aggressive line SCC9, exhibiting the least furin expression, did not. SCC15, of intermediate aggressiveness and furin expression, showed intermediate pro-VEGF-C processing. Conclusions: These findings suggest that furin is a useful marker of tumor progression and is responsible for VEGF-C processing. This in turn would enhance angiogenesis, leading to increased MVD associated with preinvasive and invasive neoplasia.
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页码:4480 / 4488
页数:9
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