Younes M, Pathak M, Finnie D, Sifers R N, Liu Y, Schwartz M R
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Anticancer Res. 2000 Sep-Oct;20(5C):3775-9.
Cancers cells utilize more glucose and amino acids than their benign counterparts. Overexpression of the facilitative glucose transporter Glut1 in human cancers was found to correlate with aggressive biologic behavior. The aim of this work was to determine whether the neutral amino acid transporter ASCT1 is expressed in human esophageal carcinomas, and to correlate the findings with Glut1 expression. Sections of formalin-fixed and paraffin-embedded tissue from 42 cases of esophageal carcinomas were entered in the study. Immunohistochemical staining was performed using a rabbit anti-ASCT1 IgG developed in our laboratory, and anti-Glut1 antibody, using standard avidin-streptavidine immunoperoxidase method. Sections of formalin-fixed and paraffin-embedded HepG2 cells were used as positive controls. The percent of ASCT1-positive cells was scored. Statistical analysis was performed using Fisher's exact test. ASCT1 immunoreactivity was cytoplasmic, whereas Glut1 was membranous. Significantly more adenocarcinomas expressed ASCT1 than squamous cell carcinomas (p < 0.0001), whereas Glut1 expression was similar in both tumor types. There was no association between the expression of either transporter and lymph node metastasis. Glut1 was expressed more often in the better differentiated than the poorly differentiated squamous carcinomas (p = 0.003). These results suggest that unlike in squamous cell carcinoma, ASCT1 plays a significant role in the recruitment of amino acids in adenocarcinoma of the esophagus, and suggest that the metabolic needs, and uptake of nutrients, are regulated differently in these two tumor types. Additional studies with larger number of patients are needed to determine the biological significance of ASCT1 expression in esophageal carcinomas.
癌细胞比其良性对应物消耗更多的葡萄糖和氨基酸。研究发现，人类癌症中促进性葡萄糖转运蛋白Glut1的过表达与侵袭性生物学行为相关。这项工作的目的是确定中性氨基酸转运蛋白ASCT1是否在人类食管癌中表达，并将研究结果与Glut1的表达相关联。本研究纳入了42例食管癌的福尔马林固定石蜡包埋组织切片。使用我们实验室制备的兔抗ASCT1 IgG和抗Glut1抗体，采用标准的抗生物素蛋白-链霉亲和素免疫过氧化物酶方法进行免疫组织化学染色。福尔马林固定石蜡包埋的HepG2细胞切片用作阳性对照。对ASCT1阳性细胞的百分比进行评分。采用Fisher精确检验进行统计分析。ASCT1免疫反应定位于细胞质，而Glut1定位于细胞膜。腺癌中ASCT1的表达明显多于鳞状细胞癌（p < 0.0001），而两种肿瘤类型中Glut1的表达相似。两种转运蛋白的表达与淋巴结转移均无关联。在高分化鳞状癌中Glut1的表达比低分化鳞状癌更常见（p = 0.003）。这些结果表明，与鳞状细胞癌不同，ASCT1在食管腺癌的氨基酸摄取中起重要作用，提示这两种肿瘤类型的代谢需求和营养物质摄取的调节方式不同。需要对更多患者进行进一步研究，以确定ASCT1在食管癌中表达的生物学意义。
