Vasohibin-1 and vasohibin-2 expression in gastric cancer cells and TAMs
Vasohibin-1 and vasohibin-2 expression in gastric cancer cells and TAMs
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DOI：
10.1007/s12032-012-0212-1
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发表时间：
2012-12-01
期刊：
影响因子：
3.4
通讯作者：
Puolakkainen, Pauli
中科院分区：
文献类型：
--
作者：
Shen, Zhanlong;Kauttu, Tuuli;Puolakkainen, Pauli
越来越多的证据表明TAM有助于肿瘤进展。最近，在内皮细胞中检测到vasohibin-1和vasohibin-2，并认为它们是内源性血管生成抑制剂。然而，尚不清楚它们是否也在癌细胞或肿瘤相关巨噬细胞（TAM）中表达。采用实时荧光定量RT-PCR方法检测了TAMs对非转移性胃癌细胞系AGS、转移性胃癌细胞系HGC-27、Hs-746 T和NCI-N87中vasohibin-1和vasohibin-2表达的影响。评价缺氧条件对血管抑制素表达的影响，并分析不同培养条件下血管抑制素-1、血管抑制素-2与VEGF-A表达的相关性。我们发现，vasohibin-1和vasohibin-2在四种胃癌细胞系和TAMs中均有表达。在正常条件下，血管组织素-1和血管组织素-2的表达显着上调TAMs在所有的胃癌细胞系。缺氧条件下，有或无TAMs培养的远处转移癌细胞株Hs-746 T中vasohibin-1和vasohibin-2的表达均显著降低（P < 0.001）。经TAM或缺氧诱导后，VASHIBIN-1和VASHIBIN-2的表达与VEGF-A的表达相关。此外，TAMs与转移癌细胞系共培养时，显示缺氧诱导的vasohibin-1上调（P < 0.05）。综上所述，vasohibin-1和vasohibin-2 mRNA在胃癌细胞和TAMs中均有表达，并且缺氧改变了它们的表达。
Accumulating evidence suggests that TAMs contribute to tumor progression. Recently, vasohibin-1 and vasohibin-2 were detected in endothelial cells and considered as intrinsic angiogenesis inhibitors. However, it is not known whether they are also expressed in cancer cells or tumor-associated macrophages (TAMs). Realtime RT-PCR was used to investigate the vasohibin-1 and vasohibin-2 expression in four gastric cancer cell lines, including a non-metastatic cell line AGS, and metastatic cell lines HGC-27, Hs-746T and NCI-N87, co-cultured with or without TAMs. The effect of hypoxic conditions on vasohibin expression was evaluated as well, and the correlation between vasohibin-1, vasohibin-2 and VEGF-A expression under different culture conditions was analyzed. We found that both vasohibin-1 and vasohibin-2 were expressed in the four gastric cancer cell lines and in TAMs. Under normal conditions, vasohibin-1 and vasohibin-2 expressions were significantly upregulated by TAMs in all the gastric cancer cell lines. Under hypoxia, both vasohibin-1 and vasohibin-2 expressions were significantly decreased in the distant metastasis cancer cell line Hs-746T, cultured with or without TAMs (P < 0.001). After induction by TAMs or hypoxia, the vasohibin-1 and vasohibin-2 expressions correlated with that of VEGF-A. In addition, TAMs, when co-cultured with the metastatic cancer cell lines, showed hypoxia-induced vasohibin-1 upregulation (P < 0.05). In conclusion, both vasohibin-1 and vasohibin-2 mRNA are expressed in gastric cancer cells and in TAMs, and their expressions are altered by hypoxia.