Koyama S, Maruyama T, Adachi S
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
J Cancer Res Clin Oncol. 1999;125(1):47-54. doi: 10.1007/s004320050241.
Quantitative analysis based on the percentage of positive cells by two-color flow cytometry was used to quantify the surface expression of epidermal growth factor receptor (EGFR), and exons v6 and v9 of CD44 splice variants on tumor. Almost all patients with primary gastric and esophageal carcinomas, and benign mucosa of the stomach and esophagus showed usually high levels of EGFR expression, a mean of approximately 60% of cells being positive. Metastatic gastric carcinoma showed significantly higher levels of EGFR expression, a mean of 80% of cells being positive. Reduced expression of EGFR was observed in irradiated esophageal carcinoma. Adenocarcinomas, including primary and metastatic lesions, or cancer cell lines of the stomach revealed consistently very low or undetectable levels of expression of exon v6 of the CD44 variant (CD44v) protein. However, CD44v containing exon v9 could be detected in normal gastric epithelium and primary gastric carcinoma as well as in six adenocarcinoma cell lines. Exon v9 is significantly overexpressed on metastatic adenocarcinoma cells obtained from malignant ascites. On the other hand, normal squamous epithelium and primary squamous cell carcinoma (SCC) of the esophagus, and two SCC cell lines showed coexpression of exons v6 and v9 of CD44v. The expression of the CD44v6 molecule was significantly reduced in the irradiated primary SCC, although CD44v9 expression on the primary SCC remained unchanged after the radiation therapy. These results suggest that up-regulation of EGFR and CD44v9 molecules on gastric carcinomas, especially metastatic adenocarcinomas, shows tumor growth and tumor progression. In addition, down-regulation of EGFR and CD44v6 molecules on irradiated esophageal carcinoma may be involved in the mechanisms suppressing tumor growth and metastatic potential.
采用基于双色流式细胞术的阳性细胞百分比进行定量分析，以量化肿瘤表皮生长因子受体（EGFR）以及CD44剪接变体的外显子v6和v9的表面表达。几乎所有原发性胃癌和食管癌患者以及胃和食管的良性黏膜通常都显示出高水平的EGFR表达，平均约60%的细胞为阳性。转移性胃癌显示出明显更高水平的EGFR表达，平均80%的细胞为阳性。在接受放疗的食管癌中观察到EGFR表达降低。包括原发性和转移性病变或胃癌细胞系在内的腺癌始终显示出CD44变体（CD44v）蛋白外显子v6的表达水平非常低或无法检测到。然而，含有外显子v9的CD44v可在正常胃上皮、原发性胃癌以及六种腺癌细胞系中检测到。外显子v9在从恶性腹水中获得的转移性腺癌细胞上显著过表达。另一方面，食管的正常鳞状上皮和原发性鳞状细胞癌（SCC）以及两种SCC细胞系显示出CD44v外显子v6和v9的共表达。放疗后的原发性SCC中CD44v6分子的表达显著降低，尽管放疗后原发性SCC上的CD44v9表达保持不变。这些结果表明，胃癌尤其是转移性腺癌上EGFR和CD44v9分子的上调显示出肿瘤生长和肿瘤进展。此外，放疗后的食管癌上EGFR和CD44v6分子的下调可能参与了抑制肿瘤生长和转移潜能的机制。
