Knockdown of hypoxia-inducible factor-1α accelerates peritoneal dissemination via the upregulation of MMP-1 expression in gastric cancer cell lines.
Knockdown of hypoxia-inducible factor-1α accelerates peritoneal dissemination via the upregulation of MMP-1 expression in gastric cancer cell lines.
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DOI：
10.3892/etm.2012.600
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发表时间：
2012-09
影响因子：
2.7
通讯作者：
Miyazaki K
中科院分区：
文献类型：
--
作者：
Hiraki M;Kitajima Y;Kai K;Nakamura J;Hashiguchi K;Noshiro H;Miyazaki K
本研究旨在探讨缺氧诱导因子-1 α（HIF-1α）在胃癌腹腔转移中的作用。利用MKN 45和MKN 74细胞系建立了HIF-1α敲低（KD）和对照（SC）胃癌细胞系。将两种细胞系直接接种于裸鼠腹腔内。比较KD和SC细胞产生的肿瘤之间播散结节的数量和重量。此外，通过分析转移相关基因的表达水平，探讨了其分子机制。与MKN 45-SC细胞系相比，MKN 45-KD细胞系表现出显著更大数量的播散性结节并形成更大的肿瘤块（p<0.05）。MKN 74-KD细胞也倾向于诱导更多数量的结节，并产生比SC细胞更重的结节。体外粘附试验揭示了不同的结果关于粘附活性的细胞外基质和单层间皮细胞的胃癌细胞来源于各种亲本细胞。KD细胞的MMP-1 mRNA表达明显高于SC细胞（p<0.01）。荧光化学研究进一步证明，与MKN 74-SC细胞相比，MKN 74-KD细胞中MMP-1的染色更强。HIF-1α的缺失可能通过上调胃癌细胞MMP-1的表达而促进胃癌细胞侵袭性腹膜转移。
This study was performed to clarify the role of hypoxia-inducible factor-1 α (HIF-1α) in the development of peritoneal dissemination in a xenograft mouse model of gastric cancer. HIF-1α knockdown (KD) and control (SC) gastric cancer cells, which were established using the MKN45 and MKN74 cell lines, were studied. The two paired cell lines were directly inoculated into the peritoneal cavity of nude mice. The number and the weight of disseminated nodules were compared between tumors generated from the KD and SC cells. In addition, the molecular mechanism was addressed through analysis of the expression levels of metastasis-related genes. The MKN45-KD cell line demonstrated significantly greater numbers of disseminated nodules and formed a larger tumor mass than the MKN45-SC cell line (p<0.05). MKN74-KD cells also tended to induce a greater number of nodules and to produce those with a heavier weight than the SC cells. An in vitro adhesion assay revealed differing results regarding the adhesion activity to extracellular matrix and monolayer mesothelium cells of the gastric cancer cells derived from the various parental cells. However, the expression of MMP-1 mRNA in the disseminated nodules was significantly increased in the KD cells compared to the SC cells derived from the two parental cell lines (p<0.01). An immunohisto-chemical study further demonstrated that there was stronger staining for MMP-1 in the MKN74-KD in comparison to MKN74-SC cells. Loss of HIF-1α may contribute to the development of aggressive peritoneal dissemination via the upregulation of MMP-1 in gastric cancer cells.
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影响因子：
8
作者：
Semenza, G. L.
通讯作者：
Semenza, G. L.
DOI：
10.1007/s005950070101
发表时间：
2000-01-01
期刊：
SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY
影响因子：
--
作者：
Mizutani, K;Kofuji, K;Shirouzu, K
通讯作者：
Shirouzu, K
DOI：
10.1007/pl00011698
发表时间：
2000-09-29
期刊：
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
影响因子：
--
作者：
Yonemura, Yutaka;Endou, Yoshio;Sasaki, Takuma
通讯作者：
Sasaki, Takuma
影响因子：
11.2
作者：
Dang, DT;Chen, F;Dang, LH
通讯作者：
Dang, LH
影响因子：
4
作者：
Pfander, D;Cramer, T;Johnson, RS
通讯作者：
Johnson, RS