CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga, Málaga, España.
J Cell Physiol. 2011 Jun;226(6):1425-32. doi: 10.1002/jcp.22668.
Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. Because cancer cells utilize glucose as their primary energy substrate, the expression and regulation of glucose transporters (GLUT) may be important in tumor development and progression. GLUT expression has not been studied previously in human osteosarcoma cell lines. Furthermore, although insulin and insulin-like growth factor (IGF-I) play an important role in cell proliferation and tumor progression, the role of these hormones on GLUT expression and glucose uptake, and their possible relation to osteosarcoma, have also not been studied. We determined the effect of insulin and IGF-I on GLUT expression and glucose transport in three well-characterized human osteosarcoma cell lines (MG-63, SaOs-2, and U2-Os) using immunocytochemical, RT-PCR and functional kinetic analyses. Furthermore we also studied GLUT isoform expression in osteosarcoma primary tumors and metastases by in situ hybridization and immunohistochemical analyses. RT-PCR and immunostaining show that GLUT1 is the main isoform expressed in the cell lines and tissues studied, respectively. Immunocytochemical analysis shows that although insulin does not affect levels of GLUT1 expression it does induce a translocation of the transporter to the plasma membrane. This translocation is associated with increased transport of glucose into the cell. GLUT1 is the main glucose transporter expressed in osteosarcoma, furthermore, this transporter is regulated by insulin in human MG-63 cells. One possible mechanism through which insulin is involved in cancer progression is by increasing the amount of glucose available to the cancer cell.
骨肉瘤是最常见的恶性骨癌类型，占原发性骨恶性肿瘤的 35%。由于癌细胞将葡萄糖作为其主要能量底物，因此葡萄糖转运蛋白（GLUT）的表达和调节可能在肿瘤的发展和进展中起重要作用。以前尚未在人骨肉瘤细胞系中研究过 GLUT 的表达。此外，尽管胰岛素和胰岛素样生长因子（IGF-I）在细胞增殖和肿瘤进展中起重要作用，但这些激素对 GLUT 表达和葡萄糖摄取的作用及其与骨肉瘤的可能关系尚未研究。我们使用免疫细胞化学，RT-PCR 和功能动力学分析，确定了胰岛素和 IGF-I 对三种特征明确的人骨肉瘤细胞系（MG-63、SaOs-2 和 U2-Os）中 GLUT 表达和葡萄糖转运的影响。此外，我们还通过原位杂交和免疫组织化学分析研究了骨肉瘤原发性肿瘤和转移瘤中 GLUT 同工型的表达。RT-PCR 和免疫染色表明，GLUT1 是细胞系和组织中表达的主要同工型。免疫细胞化学分析表明，尽管胰岛素不会影响 GLUT1 表达水平，但它确实会诱导转运蛋白向质膜易位。这种易位与葡萄糖向细胞内的转运增加有关。GLUT1 是骨肉瘤中表达的主要葡萄糖转运蛋白，此外，这种转运蛋白在人 MG-63 细胞中受胰岛素调节。胰岛素参与癌症进展的一种可能机制是通过增加癌细胞可用的葡萄糖量。
