Vascular endothelial growth factor synthesis by human omental mesothelial cells is augmented by fibroblast growth factor-2: Possible role of mesothelial cell on the development of peritoneal metastasis
Vascular endothelial growth factor synthesis by human omental mesothelial cells is augmented by fibroblast growth factor-2: Possible role of mesothelial cell on the development of peritoneal metastasis
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DOI：
10.1016/s0022-4804(03)00307-x
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发表时间：
2003-11-01
影响因子：
2.2
通讯作者：
Nagawa, H
中科院分区：
文献类型：
--
作者：
Sako, A;Kitayama, J;Nagawa, H
虽然腹膜转移是决定胃肠癌患者预后的重要因素，但其机制尚未明确。人腹膜间皮细胞（HPMC）是对抗播散性肿瘤细胞的第一线。最近的报告表明间皮细胞能够分泌各种细胞因子和生长因子。在这项研究中，我们从手术切除的网膜组织中分离出人间皮细胞，并检查了两种主要血管生成因子——血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（FGF-2）的产生和相互作用。静态 HPMC 产生大量 VEGF，其水平几乎与肿瘤细胞相同。有趣的是，根据 Northern 印迹和 ELISA 测定，向培养物中添加 FGF-2 以剂量依赖性方式显着增加 VEGF 的 mRNA 合成和蛋白质分泌。添加 0.5 ng/mL FGF-2 足以刺激 VEGF 产生，且效果在 5 ng/mL 时达到稳定水平。逆转录聚合酶链反应（RT-PCR）方法表明HPMC来源的VEGF主要由VEGF（121）和VEGF（165）组成，这两种形式主要是可溶性形式。这些数据表明，由于 VEGF 的产生，HPMC 有助于转移的发展和恶性腹水的积累，特别是在 VEGF 表达量不足的癌症中。 (C) 2003 Elsevier Inc. 保留所有权利。
Although peritoneal metastasis is an important factor determining the prognosis of patients with gastrointestinal cancer, the mechanisms have not yet been clearly defined. Human peritoneal mesothelial cells (HPMC) are the first line against disseminated tumor cells. Recent reports have shown that mesothelial cells are capable of secreting various cytokines and growth factors. In this study, we isolated human mesothelial cells from surgically resected omental tissue and examined the production and interaction of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). Quiescent HPMC produced a considerable amount of VEGF at almost the same level as tumor cells. Interestingly, addition of FGF-2 to the culture significantly increased the mRNA synthesis and protein secretion of VEGF in a dose-dependent manner, as determined by Northern blot and ELISA. The addition of 0.5 ng/mL FGF-2 was enough to stimulate VEGF production, and the effect reached a plateau at 5 ng/mL. Reverse-transcribed polymerase chain reaction (RT-PCR) method clarified that the HPMC-derived VEGF consisted mostly of VEGF(121) and VEGF(165), which are both predominantly soluble forms. These data suggest that HPMC contribute to the development of metastases and the accumulation of malignant ascites due to the production of VEGF, especially in cancers that do not express enough amount of VEGF. (C) 2003 Elsevier Inc. All rights reserved.