Direct cancer-stromal interaction increases fibroblast proliferation and enhances invasive properties of scirrhous-type gastric carcinoma cells.
Direct cancer-stromal interaction increases fibroblast proliferation and enhances invasive properties of scirrhous-type gastric carcinoma cells.
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DOI：
10.1038/sj.bjc.6605309
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发表时间：
2009-10-20
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
scirrhouse型胃癌（SGC）表现为广泛的粘膜下纤维化，患者预后极差。我们研究了癌间质相互作用在SGC组织发生中的重要性。胃成纤维细胞NF-25和肠成纤维细胞NF-j2与sgc来源的（HSC-39）或非sgc来源的（HSC-57和HSC-64）细胞共培养。为了鉴定NF-25中上调或下调的基因，进行了互补DNA （cDNA）微阵列分析。采用抗血管细胞粘附分子-1 （VCAM-1）抗体进行细胞生长试验和免疫组化。此外，利用western blot和逆转录聚合酶链反应研究了与NF-25成纤维细胞相互作用对HSC-39细胞的影响。共培养时，HSC-39细胞能刺激NF-25的生长，但不能刺激NF-j2的生长。在NF-25成纤维细胞中发现了VCAM-1的诱导作用，当与HSC-39共培养时，这种诱导作用是特异性的，而与非sgc来源的HSC-57和HSC-64细胞共培养时则没有。VCAM-1中和抗体以剂量依赖性方式抑制NF-25的生长。在组织样本中，sgc源性成纤维细胞中VCAM-1的阳性免疫反应性明显高于非sgc源性成纤维细胞。此外，与NF-25成纤维细胞的相互作用不仅诱导了HSC-39细胞的上皮-间质过渡样变化，而且还诱导了基质金属蛋白酶相关基因的表达。SGC细胞与胃成纤维细胞之间的直接相互作用建立了肿瘤微环境，增强了SGC的侵袭性。
Scirrhous-type gastric carcinoma (SGC) exhibits an extensive submucosal fibrosis and extremely poor patient prognosis. We investigated the importance of the cancer–stromal interaction in the histogenesis of SGC. Gastric fibroblasts NF-25 and intestinal fibroblasts NF-j2 were co-cultured with SGC-derived (HSC-39) or non-SGC-derived (HSC-57 and HSC-64) cells. To identify genes that are up- or downregulated in NF-25, complementary DNA (cDNA) microarray analysis was performed. The antibody against vascular-cell adhesion molecule-1 (VCAM-1) was used for cell growth test and immunohistochemistry. Moreover, the impact of interaction with NF-25 fibroblasts on HSC-39 cells was investigated using western blot and reverse transcription-polymerase chain reaction. HSC-39 cells stimulated growth of NF-25 but not NF-j2 when co-cultured. Induction of VCAM-1 in NF-25 fibroblasts was identified, which was specific when co-cultured with HSC-39 but not with non-SGC-derived HSC-57 and HSC-64 cells. Neutralising antibody to VCAM-1 suppressed NF-25 growth in dose-dependent manners. In tissue samples, positive immunoreactivity of VCAM-1 in SGC-derived fibroblasts was significantly higher than that in non-SGC-derived fibroblasts. Furthermore, interaction with NF-25 fibroblasts not only induced the epithelial–mesenchymal transition-like change, but also expressions of matrix metalloproteinase- related genes in HSC-39 cells. Direct interaction between SGC cells and gastric fibroblasts establishes the tumour microenvironment and reinforces the aggressiveness of SGC.
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N-钙粘着蛋白在乳腺癌细胞中的外源表达会诱导细胞迁移，侵袭和转移。
影响因子：
7.8
作者：
Hazan, R B;Phillips, G R;Qiao, R F;Norton, L;Aaronson, S A
通讯作者：
Aaronson, S A
影响因子：
8.4
作者：
Alexiou, D;Karayiannakis, AJ;Tsigris, C
通讯作者：
Tsigris, C
影响因子：
11.2
作者：
Hwang, Rosa F.;Moore, Todd;Logsdon, Craig D.
通讯作者：
Logsdon, Craig D.
影响因子：
64.8
作者：
SATO, H;TAKINO, T;SEIKI, M
通讯作者：
SEIKI, M
影响因子：
29.4
作者：
Nakamura, Kazunori;Yashiro, Masakazu;Hirakawa, Kosei
通讯作者：
Hirakawa, Kosei