Gamma-glutamyl transferase expression in higher-grade astrocytic glioma
Gamma-glutamyl transferase expression in higher-grade astrocytic glioma
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DOI：
10.1080/028418601750288271
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发表时间：
2001-01-01
期刊：
影响因子：
3.1
通讯作者：
Rainov, NG
中科院分区：
文献类型：
--
作者：
Schäfer, C;Fels, C;Rainov, NG
已在一系列人类恶性肿瘤中检测到γ-谷氨酰转移酶（GGT）表达增加，并认为其与肿瘤增殖和治疗耐药性有关。由于GGT表达及其在恶性胶质瘤生物学中的作用在很大程度上仍不清楚，我们通过用单克隆抗GGT抗体（138 H11）对26个较高级别的人类星形胶质细胞胶质瘤（WHO III级和IV级）进行免疫染色来研究这一现象。此外，人胰腺GGT cDNA用于脂质体介导的9 L胶质肉瘤细胞的转染。在含有不同量的必需氨基酸和/或细胞毒性剂的培养基中培养GGT表达细胞和对照9 L细胞。MTT法检测细胞活力。肿瘤标本的免疫组化染色表明，GGT表达是一个常见的功能，高级别的人类星形胶质细胞瘤，但不是正常的脑组织。人类肿瘤中有6例III级星形细胞瘤，12例IV级星形细胞瘤（多形性胶质母细胞瘤，GBM）的情况下，强烈GGT阳性。在细胞培养模型中，9 L-GGT细胞在半胱氨酸缺陷培养基中比对照细胞具有生长优势，但在标准或无谷氨酰胺培养基中没有。在含有烷基化药物BCNU（5-200 μ g/ml）的培养基中，两个克隆的活细胞数量没有显着差异。总之，GGT在高比例的人WHO III级星形细胞瘤和GBM中表达，但在正常脑组织中不表达。该分子似乎在体内条件下给予肿瘤细胞适度的生长优势。
Increased expression of gamma -glutamyltransferase (GGT) has been detected in a range of human malignancies and is thought to be involved in neoplastic proliferation and treatment resistance. Since GGT expression and its role in malignant glioma biology remain largely unknown, we investigated this phenomenon by immunostaining 26 higher-grade human astrocytic gliomas (WHO grades III and IV) with a monoclonal anti-GGT-antibody (138H11). Further, human pancreatic GGT cDNA was used for liposome-mediated transfection of 9L gliosarcoma cells. GGT-expressing and control 9L cells were cultured in media containing different amounts of essential amino acids and/or cytotoxic agents. Cell viability was evaluated by microplate MTT assay. Immunohistochemical staining of tumor specimens demonstrated that GGT expression is a frequent feature of higher-grade human astrocytic gliomas, but not of normal brain tissue. Human tumors were strongly GGT-positive in 6 of 7 cases of grade III astrocytoma, and in 12 of 19 grade IV astrocytoma (glioblastoma multiforme, GBM) cases. In the cell culture model, 9L-GGT cells had a growth advantage over control cells in cysteine-deficient medium, but not in standard or glutamine-free medium. No significant difference in numbers of viable cells of either clone was found in media containing the alkylating drug BCNU (5-200 mug/ml). In conclusion, GGT is expressed in a high percentage of human WHO grade III astrocytomas and GBM, but not in normal brain tissue. This molecule seems to give neoplastic cells a moderate growth advantage under in vivo conditions.