Noguchi Y, Marat D, Saito A, Yoshikawa T, Doi C, Fukuzawa K, Tsuburaya A, Satoh S, Ito T
First Department of Surgery, Yokohama City University School of Medicine, Japan.
Hepatogastroenterology. 1999 Jul-Aug;46(28):2683-9.
BACKGROUND/AIMS: Although cancer cells are known to have an increased rate of glucose metabolism, the complete mechanism for increased glucose uptake in tumor cells is unknown.
The presence of mRNA for 5 facilitative glucose transporter (GLUT) isoforms was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in paired samples of normal gastric mucosa and gastric tumor from 20 individuals. Expression of GLUT proteins was immunohistochemically determined in 70 resected gastric cancer specimens.
By using RT-PCR, GLUT2 mRNA was detected in 80% of normal gastric mucosal samples, while GLUT4 mRNA was seen in only 40%, GLUT1 mRNA was not detected in normal gastric mucosa. In gastric carcinoma samples, GLUT1 mRNA was detected in 19 out of 20 cases (95%) and GLUT2, GLUT3, and GLUT4 mRNAs in all samples. By immunohistochemistry, GLUT1 protein was detected in 19% of the tumors. A majority of tumors (61%) expressed 1 or more transporter protein. The presence of GLUT1 protein in a tumor was positively correlated with the tumor's invasion into the gastric wall, lymphatics or blood vessels and with lymph node metastases. The post-operative survival of patients with tumor expressing GLUT1 protein was significantly worse than those with tumor without GLUT1 protein.
Gastric cancer cells may acquire the ability to produce GLUT1 mRNA by malignant transformation. Increased expression of the high-affinity glucose transporters, GLUT1 and/or GLUT4, in tumor cells may drain glucose preferentially to the tumor at the expense of the tumor-bearing host.
背景/目的:尽管已知癌细胞的葡萄糖代谢率增加,但肿瘤细胞中葡萄糖摄取增加的完整机制尚不清楚。
采用逆转录-聚合酶链反应(RT-PCR)对20例个体的正常胃黏膜和胃肿瘤配对样本中5种易化葡萄糖转运体(GLUT)亚型的mRNA表达进行评估。对70例切除的胃癌标本进行免疫组织化学检测GLUT蛋白的表达。
通过RT-PCR,在80%的正常胃黏膜样本中检测到GLUT2 mRNA,而仅在40%的样本中检测到GLUT4 mRNA,在正常胃黏膜中未检测到GLUT1 mRNA。在胃癌样本中,20例中有19例(95%)检测到GLUT1 mRNA,所有样本中均检测到GLUT2、GLUT3和GLUT4 mRNA。通过免疫组织化学,在19%的肿瘤中检测到GLUT1蛋白。大多数肿瘤(61%)表达1种或更多种转运蛋白。肿瘤中GLUT1蛋白的存在与肿瘤侵犯胃壁、淋巴管或血管以及淋巴结转移呈正相关。表达GLUT1蛋白的肿瘤患者术后生存率明显低于不表达GLUT1蛋白的肿瘤患者。
胃癌细胞可能通过恶性转化获得产生GLUT1 mRNA的能力。肿瘤细胞中高亲和力葡萄糖转运体GLUT1和/或GLUT4的表达增加可能优先将葡萄糖引流至肿瘤,而以荷瘤宿主为代价。