Hypoxia affects in vitro growth of newly established cell lines from patients with malignant pleural mesothelioma

Hypoxia affects in vitro growth of newly established cell lines from patients with malignant pleural mesothelioma
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DOI:
10.2220/biomedres.34.13
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发表时间:
2013-02-01
影响因子:
1.2
通讯作者:
Hamada, Jun-ichi
Hamada, Jun-ichi
中科院分区:
医学4区
文献类型:
--
作者:
Goudarzi, Houman;Hida, Yasuhiro;Hamada, Jun-ichi

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人恶性胸膜间皮瘤(MPM)侵袭性强,预后差。为了早期诊断和制定新的治疗策略,有必要更好地了解MPM的生物学特性。在这项研究中,我们从MPM患者的胸腔积液中建立了两种细胞系。两种细胞系均表达间皮瘤的肿瘤标志物,如间皮素、podoplanin、WT1、calretinin和角蛋白5/6,而不表达常被用作肺腺癌标志物的CEA或TTF-1。这些细胞系含有野生型TP53,产生透明质酸,并且没有感染SV40。当这两种细胞系在低氧(1% O-2)条件下培养时,它们对低氧条件表现出特殊的反应,与在常氧条件(21% O-2)下培养的细胞不同。也就是说,两种细胞系在缺氧条件下都能激发单细胞形成集落的能力(电镀效率和克隆效率)。另一方面,当细胞密度相对较高时,两种细胞系的生长,无论锚定依赖还是独立,在缺氧条件下都有所下降。低氧和常氧条件下细胞生长的差异,以及细胞密度对细胞生长的影响,可能为MPM的诊断和治疗提供新的思路。
Human malignant pleural mesothelioma (MPM) is highly aggressive, and its prognosis is very poor. For an early diagnosis of MPM and developing new therapeutic strategies against the malignancy, it is necessary to better understand biological characteristics of MPM. In this study, we established two cell lines from pleural effusions derived from patients with MPM. Both cell lines expressed tumor markers of mesothelioma such as mesothelin, podoplanin, WT1, calretinin and keratin 5/6 whereas they did not express either CEA or TTF-1 which are often used as markers of lung adenocarcinoma. The cell lines harboured wild-type TP53, produced hyaluronic acid, and were not infected with SV40. When these two cell lines were cultured under hypoxia (1% O-2), they showed particular responses to the hypoxic condition, distinct from those to normoxic condition (21% O-2). Namely, the ability to form a colony originating from a single cell (plating efficiency and cloning efficiency) was stimulated under hypoxia in both cell lines. On the other hand, when the assays of cell growth were started at a relatively high cell density, the growth of both cell lines, regardless of anchorage-dependent or -independent, decreased under hypoxia. The differences of their growth between under hypoxia and under normoxia, and those depending on the cell density, may provide useful hints for developing a new strategy for diagnosis or therapy of MPM.