Lalla Rajesh V, Boisoneau David S, Spiro Jeffrey D, Kreutzer Donald L
Division of Oral Medicine, Department of Oral Diagnosis, University of Connecticut Health Center, Farmington, Conn., USA.
Arch Otolaryngol Head Neck Surg. 2003 Aug;129(8):882-8. doi: 10.1001/archotol.129.8.882.
Angiogenesis is essential for the growth of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Angiogenesis is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) 1, 2, and 3 known to be located on vascular endothelial cells (VECs). We hypothesize that VEGFRs are also expressed on HNSCC tumor cells in vitro and in vivo and likely control tumor function in vivo.
Immunohistochemical analysis for VEGFR-1 (n = 13), VEGFR-2 (n = 21), and VEGFR-3 (n = 16) was performed on human HNSCC tumor samples. Specimens were analyzed for receptor expression and staining intensity. A cultured oral SCC cell line (SCC-25) and a pharyngeal SCC cell line (FADU) were also studied for receptor expression.
The HNSCC tumor cells expressed VEGFR-1, VEGFR-2, and VEGFR-3 in all specimens evaluated. Staining for all 3 receptors was also found on tumor-associated macrophages and fibroblasts, except that VEGFR-2 was not present on fibroblasts. Staining intensity for VEGFR-1 and VEGFR-2 was significantly higher in tumor cells and macrophages than in VECs stained for the same receptor. Both cultured HNSCC cell lines demonstrated expression of all 3 receptors.
This represents the first report of all 3 VEGFRs being expressed by HNSCC cells. These findings indicate that VEGF may be an autocrine regulator of tumor cell activity in addition to its known angiogenic effects on VECs. The presence of VEGFRs on tumor-associated macrophages and fibroblasts contributes to the complexity of the VEGF/VEGFR system in human cancer.
血管生成对于实体瘤的生长至关重要，包括头颈部鳞状细胞癌（HNSCC）。血管生成受血管生成因子如血管内皮生长因子（VEGF）及其受体（VEGFRs）1、2和3的调节，这些因子已知位于血管内皮细胞（VECs）上。我们假设VEGFRs在体外和体内的HNSCC肿瘤细胞上也有表达，并可能在体内控制肿瘤功能。
对人类HNSCC肿瘤样本进行VEGFR-1（n = 13）、VEGFR-2（n = 21）和VEGFR-3（n = 16）的免疫组织化学分析。对标本进行受体表达和染色强度分析。还研究了一种培养的口腔鳞状细胞癌细胞系（SCC-25）和一种咽鳞状细胞癌细胞系（FADU）的受体表达情况。
在所有评估的标本中，HNSCC肿瘤细胞均表达VEGFR-1、VEGFR-2和VEGFR-3。在肿瘤相关巨噬细胞和成纤维细胞上也发现了所有3种受体的染色，不过成纤维细胞上不存在VEGFR-2。VEGFR-1和VEGFR-2在肿瘤细胞和巨噬细胞中的染色强度明显高于相同受体染色的VECs。两种培养的HNSCC细胞系均显示出所有3种受体的表达。
这是关于HNSCC细胞表达所有3种VEGFRs的首次报道。这些发现表明，VEGF除了对VECs具有已知的血管生成作用外，可能还是肿瘤细胞活性的自分泌调节因子。肿瘤相关巨噬细胞和成纤维细胞上VEGFRs的存在增加了人类癌症中VEGF/VEGFR系统的复杂性。
