Kellokumpu Sakari, Sormunen Raija, Kellokumpu Ilmo
Department of Biochemistry, University of Oulu, P.O. Box 3000, FIN-90014, Oulu, Finland.
FEBS Lett. 2002 Apr 10;516(1-3):217-24. doi: 10.1016/s0014-5793(02)02535-8.
Abnormal glycosylation of cellular glycoconjugates is a common phenotypic change in many human tumors. Here, we explore the possibility that an altered Golgi pH may also be responsible for these cancer-associated glycosylation abnormalities. We show that a mere dissipation of the acidic Golgi pH results both in increased expression of some cancer-associated carbohydrate antigens and in structural disorganization of the Golgi apparatus in otherwise normally glycosylating cells. pH dependence of these alterations was confirmed by showing that an acidification-defective breast cancer cell line (MCF-7) also displayed a fragmented Golgi apparatus, whereas the Golgi apparatus was structurally normal in its acidification-competent subline (MCF-7/AdrR). Acidification competence was also found to rescue normal glycosylation potential in MCF-7/AdrR cells. Finally, we show that abnormal glycosylation is also accompanied by similar structural disorganization and fragmentation of the Golgi apparatus in colorectal cancer cells in vitro and in vivo. These results suggest that an inappropriate Golgi pH may indeed be responsible for the abnormal Golgi structure and lowered glycosylation potential of the Golgi apparatus in malignant cells.
细胞糖缀合物的异常糖基化是许多人类肿瘤中常见的表型变化。在此，我们探讨了高尔基体pH改变也可能导致这些与癌症相关的糖基化异常的可能性。我们发现，仅仅是酸性高尔基体pH的消散，就会导致一些与癌症相关的碳水化合物抗原表达增加，以及在其他方面正常进行糖基化的细胞中高尔基体结构紊乱。通过显示酸化缺陷的乳腺癌细胞系（MCF-7）也表现出高尔基体碎片化，而其具有酸化能力的亚系（MCF-7/AdrR）中高尔基体结构正常，证实了这些改变对pH的依赖性。还发现酸化能力可挽救MCF-7/AdrR细胞中的正常糖基化潜力。最后，我们表明，在体外和体内的结肠癌细胞中，异常糖基化也伴随着高尔基体类似的结构紊乱和碎片化。这些结果表明，不适当的高尔基体pH可能确实是导致恶性细胞中高尔基体结构异常和高尔基体糖基化潜力降低的原因。
