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原发性人结肠腺癌细胞(SW480)及其淋巴结转移衍生物(SW620)中的多胺代谢

Polyamine metabolism in primary human colon adenocarcinoma cells (SW480) and their lymph node metastatic derivatives (SW620).

作者信息

Duranton B, Holl V, Schneider Y, Carnesecchi S, Gossé F, Raul F, Seiler N

机构信息

Laboratory of Nutritional Cancer Prevention, INSERM U392, Strasbourg, France.

出版信息

Amino Acids. 2003;24(1-2):63-72. doi: 10.1007/s00726-002-0333-5.

Abstract

The natural polyamines are multifunctional constituents of all eucaryotic cells. The objective of this work was to compare aspects of polyamine metabolism in two related cell lines with the idea to investigate whether metabolic differences can be attributed to functional differences of the cells. The human colon carcinoma-derived cell lines SW480 and SW620 were chosen as models. SW480 cells were isolated from the primary tumour, SW620 cells from a lymph node of the same patient. SW620 cells grow faster, and the key regulatory enzymes of polyamine biosynthesis (ODC and AdoMetDC) are more active in the metastatic cells. Moreover, their ability to accumulate polyamines from the environment is more important than of SW480 cells. Likewise polyamine concentrations were markedly higher in SW620 cells, although they are much smaller than SW480 cells, and have a particularly small cytoplasmic space. Both cell lines show a striking diminution of ODC and AdoMetDC activities and changes in the polyamine patterns at the transition from exponential to non-exponential growth--most probably as a consequence of high cell density. Depletion of putrescine and spermidine due to inactivation of ODC by DFMO causes accumulation of cells in G1, and a proportional decrease of S-phase cells in both cell lines. Based on morphologic and other criteria SW480 and SW620 cells were typified as poorly differentiated. In agreement with their low grade of differentiation they exhibit a low alkaline phosphatase activity. However, the time-dependent decrease of alkaline phosphatase is not typical of differentiation patterns of other adenocarcinoma-derived cell lines or of normal enterocytes. The high capacity of de novo polyamine biosynthesis and of polyamine uptake is presumably a prerequisite for the rapid growth and invasiveness. The fact that these properties were more accentuated in the case of SW620 cells and paralleled enhanced metastatic properties indicate relationships between basic parameters of polyamine metabolism and malignancy.

摘要

天然多胺是所有真核细胞的多功能组成成分。本研究的目的是比较两种相关细胞系中多胺代谢的各个方面,以探讨代谢差异是否可归因于细胞的功能差异。选用人结肠癌衍生细胞系SW480和SW620作为模型。SW480细胞从原发性肿瘤中分离得到,SW620细胞则来自同一患者的淋巴结。SW620细胞生长更快,多胺生物合成的关键调节酶(鸟氨酸脱羧酶和S-腺苷甲硫氨酸脱羧酶)在转移细胞中更活跃。此外,它们从环境中积累多胺的能力比SW480细胞更为重要。同样,SW620细胞中的多胺浓度明显更高,尽管它们比SW480细胞小得多,且细胞质空间特别小。两种细胞系在从指数生长转变为非指数生长时,鸟氨酸脱羧酶和S-腺苷甲硫氨酸脱羧酶的活性均显著降低,多胺模式也发生变化——这很可能是高细胞密度的结果。由于DFMO使鸟氨酸脱羧酶失活导致腐胺和亚精胺耗竭,使得两种细胞系中的细胞在G1期积累,S期细胞比例相应下降。根据形态学和其他标准,SW480和SW620细胞被归类为低分化细胞。与它们的低分化程度一致,它们的碱性磷酸酶活性较低。然而,碱性磷酸酶随时间的下降并非其他腺癌衍生细胞系或正常肠上皮细胞分化模式的典型特征。多胺从头生物合成和多胺摄取的高能力可能是快速生长和侵袭性的先决条件。这些特性在SW620细胞中更为突出,并与增强的转移特性平行,这一事实表明多胺代谢的基本参数与恶性肿瘤之间存在关联。

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