Brown R S, Wahl R L
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028.
Cancer. 1993 Nov 15;72(10):2979-85. doi: 10.1002/1097-0142(19931115)72:10<2979::aid-cncr2820721020>3.0.co;2-x.
Breast cancers have higher than normal glucose metabolism, but the mechanism of glucose entry into these tumors is not well understood.
The expression of five facilitative glucose transporters, Glut-1 (erythrocyte type), Glut-2 (liver type), Glut-3 (brain type), Glut-4 (muscle/fat type), and Glut-5 (small intestine type), was studied by immunohistochemistry of paraffin sections from 12 primary human breast cancers and 8 lymph node metastases from 2 patients. Rat tissues known to express these glucose transporters were used as controls.
All the primary breast cancers and the lymph node metastases were positive for Glut-1. This transporter was expressed on the cell membrane and in the cytoplasm of the tumor cells, but exhibited marked intratumoral and intertumoral variability in the proportions of positive cells and the intensity of staining. Staining of the normal mammary epithelium, if present, was much lower than observed in tumor cells from the same patient. Glut-2 was expressed in all of the tumors, but the intensity of staining was not consistently stronger than that seen in healthy breast. Clusters of Glut-4-positive granule were observed in cells in six of the tumors. None of the tumors or the healthy breast in the tissues studied expressed Glut-3 or Glut-5.
Higher expression of the glucose transporter Glut-1 by breast cancer cells compared with the healthy breast tissue is common. Increased glucose transporter protein expression may contribute to the increased uptake of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) by these tumors observed by positron emission tomography (PET) imaging.
乳腺癌具有高于正常水平的葡萄糖代谢,但葡萄糖进入这些肿瘤的机制尚未完全明确。
通过免疫组织化学方法,对12例原发性人类乳腺癌和2例患者的8个淋巴结转移灶的石蜡切片进行研究,检测5种易化葡萄糖转运蛋白,即葡萄糖转运蛋白1(红细胞型)、葡萄糖转运蛋白2(肝型)、葡萄糖转运蛋白3(脑型)、葡萄糖转运蛋白4(肌肉/脂肪型)和葡萄糖转运蛋白5(小肠型)的表达情况。已知表达这些葡萄糖转运蛋白的大鼠组织用作对照。
所有原发性乳腺癌和淋巴结转移灶的葡萄糖转运蛋白1均呈阳性。该转运蛋白在肿瘤细胞膜和细胞质中表达,但在阳性细胞比例和染色强度方面,肿瘤内和肿瘤间存在显著差异。正常乳腺上皮(若存在)的染色远低于同一患者肿瘤细胞的染色。所有肿瘤均有葡萄糖转运蛋白2表达,但染色强度并不始终强于健康乳腺组织。在6个肿瘤的细胞中观察到葡萄糖转运蛋白4阳性颗粒簇。在所研究的组织中,肿瘤和健康乳腺均未表达葡萄糖转运蛋白3或葡萄糖转运蛋白5。
与健康乳腺组织相比,乳腺癌细胞中葡萄糖转运蛋白1的表达较高是常见现象。葡萄糖转运蛋白表达增加可能有助于正电子发射断层扫描(PET)成像观察到的这些肿瘤对2-[18F]-氟-2-脱氧-D-葡萄糖(FDG)摄取增加。