The significance of MMP-1 and MMP-2 in peritoneal disseminated metastasis of gastric cancer

The significance of MMP-1 and MMP-2 in peritoneal disseminated metastasis of gastric cancer
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DOI:
10.1007/s005950070101
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发表时间:
2000-01-01
期刊:
SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY
影响因子:
--
通讯作者:
Shirouzu, K
Shirouzu, K
中科院分区:
其他
文献类型:
--
作者:
Mizutani, K;Kofuji, K;Shirouzu, K

文献摘要

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本研究的目的是阐明基质金属蛋白酶(MMPs),胶原酶(MMP-1)和明胶酶A(MMP-2),这两者都是已知参与胃癌的发展,在腹膜传播的作用。采用酶联免疫吸附法测定体外培养的间皮细胞和癌细胞模拟腹膜播散的混合培养上清液中MMP-1和MMP-2的浓度。与非接触混合培养或单纯间皮细胞培养相比,两者混合后MMP-1的表达明显增加。这些结果表明,通过与癌细胞接触,来自间皮细胞的MMP-1的产生增加。为了阐明MMP-1和MMP-2对胃癌侵袭的作用,使用基质胶进行侵袭测定。经抗MMP-1单克隆抗体或抗MMP-2单克隆抗体处理后,穿透基质胶的癌细胞数量明显减少,表明来源于间皮细胞的MMP-1和MMP-2对胃癌侵袭有较强的反应。总之,由于MMP-1对癌细胞的刺激表现出旁分泌样作用,因此它似乎在腹膜播散的进展中起重要作用。
The purpose of this study was to clarify the role of the matrix metalloproteinases (MMPs), collagenase (MMP-1), and gelatinase A (MMP-2), both of which are known to be involved in the development of gastric cancer, in peritoneal dissemination. The concentrations of MMP-1 and MMP-2 in the supernatant of mixed culture simulated peritoneal dissemination were measured in vitro with mesothelial cells and cancer cells using an enzyme-linked immunosorbent assay. The concentration of MMP-1 ir,creased significantly after the contact culture was mixed with these two cells, in comparison with the non-contact mixed culture or the mesothelial cell culture alone. These results demonstrate that the production of MMP-1 derived from mesothelial cells was increased by contact with cancer cells. To clarify the effect of MM P-l and MMP-2 on gastric cancer invasion, an invasion assay using matrigel was performed. After treatment with anti-MMP-1 monoclonal antibody (mAb) or anti-MMP-2 mAb, the number of matrigel-penetrating cancer cells was significantly reduced, indicating that MMP-1 and MMP-2 derived from mesothelial cells had a strong reaction to gastric cancer invasion. In conclusion, as MMP-1 showed a paracrine-like action responding to stimulus from cancer cells, it seemed to play an important role in the progression of peritoneal dissemination.