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人恶性胶质瘤中血小板衍生生长因子样蛋白产生及相应受体表达的克隆变异

Clonal variation in the production of a platelet-derived growth factor-like protein and expression of corresponding receptors in a human malignant glioma.

作者信息

Nistér M, Heldin C H, Westermark B

出版信息

Cancer Res. 1986 Jan;46(1):332-40.

PMID:2998609
Abstract

Two cell lines (U-343 MG and U-343 MGa) with different phenotypic characteristics were established from the same human glioblastoma multiforme biopsy. Previous studies have shown that a clonal derivative (Cl 2) of the U-343 MGa line produces a PDGF-like growth factor. In the present investigation glioma PDGF production and 125I-PDGF binding were found to be differently expressed in U-343 MG, U-343 MGa, and U-343 MGa Cl 2 cultures, providing evidence for a clonal variation in these properties. In order to investigate this point further, several clones were derived from low (23 clones) and high (30 clones) passage U-343 MGa cultures, as well as from U-343 MGa Cl 2 cells (30 clones). The clones could be divided into 4 groups according to morphology and growth pattern. A determination of the amount of PDGF receptor competing activity in serum-free conditioned media gave evidence for a clonal variation in the production of glioma PDGF, corresponding to 0-87 ng of authentic PDGF per ml. There was also a considerable range in 125I-PDGF binding (0-44 fmol of tracer bound per 10(6) cells). Scatchard plots performed on two clones confirmed the presence of saturable, high affinity PDGF receptors. High passage cultures were found to give rise to a higher number of high producing clones than did low passage cultures. There appeared to be a negative correlation between production of glioma PDGF and binding of 125I-PDGF, probably due to the receptor blocking activity of the endogenous growth factor. However, the presence of clones, apparently devoid of both glioma PDGF production and 125I-PDGF binding, suggests a true clonal variation in these two parameters. The growth rate in serum-free medium was found to correlate fairly well to the extent of glioma PDGF production. Production of glioma PDGF was found to have a morphological correlate and be most prominent among clones of "immature" looking, tightly growing cells. Clones that had large star-shaped cells with some resemblance to normal glia-like cells in culture were found to have a low production and a high 125I-PDGF binding capacity.

摘要

从同一例多形性胶质母细胞瘤活检样本中建立了具有不同表型特征的两种细胞系(U - 343 MG和U - 343 MGa)。先前的研究表明,U - 343 MGa细胞系的一个克隆衍生物(Cl 2)能产生一种血小板源性生长因子(PDGF)样生长因子。在本研究中,发现胶质瘤PDGF的产生及125I - PDGF结合在U - 343 MG、U - 343 MGa和U - 343 MGa Cl 2培养物中的表达存在差异,这为这些特性中的克隆变异提供了证据。为了进一步研究这一点,从传代次数少的(23个克隆)和传代次数多的(30个克隆)U - 343 MGa培养物以及U - 343 MGa Cl 2细胞(30个克隆)中获得了几个克隆。这些克隆可根据形态和生长模式分为4组。对无血清条件培养基中PDGF受体竞争活性量的测定为胶质瘤PDGF产生中的克隆变异提供了证据,相当于每毫升0 - 87纳克的真实PDGF。125I - PDGF结合也有相当大的范围(每10(6)个细胞结合0 - 44飞摩尔示踪剂)。对两个克隆进行的Scatchard图分析证实了存在可饱和的、高亲和力的PDGF受体。发现传代次数多的培养物比传代次数少的培养物产生更多高产量的克隆。胶质瘤PDGF的产生与125I - PDGF的结合之间似乎存在负相关,这可能是由于内源性生长因子的受体阻断活性。然而,存在明显既不产生胶质瘤PDGF也不结合125I - PDGF的克隆,这表明这两个参数存在真正的克隆变异。发现在无血清培养基中的生长速率与胶质瘤PDGF的产生程度有较好的相关性。发现胶质瘤PDGF的产生与形态学相关,在外观“不成熟”、紧密生长的细胞克隆中最为突出。在培养中具有大的星形细胞且与正常胶质样细胞有些相似的克隆,其产量低且125I - PDGF结合能力高。

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Clonal variation in the production of a platelet-derived growth factor-like protein and expression of corresponding receptors in a human malignant glioma.人恶性胶质瘤中血小板衍生生长因子样蛋白产生及相应受体表达的克隆变异
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