p37 from Mycoplasma hyorhinis promotes cancer cell invasiveness and metastasis through activation of MMP-2 and followed by phosphorylation of EGFR
p37 from Mycoplasma hyorhinis promotes cancer cell invasiveness and metastasis through activation of MMP-2 and followed by phosphorylation of EGFR
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DOI：
10.1158/1535-7163.mct-07-2191
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发表时间：
2008-03-01
影响因子：
5.7
通讯作者：
Shou, Chengchao
中科院分区：
文献类型：
--
作者：
Gong, Manman;Meng, Lin;Shou, Chengchao
胃癌组织中的高支原体感染表明支原体感染与肿瘤发生之间可能存在关联。通过使用稳定表达猪鼻支原体主要免疫原p37的人胃癌细胞AGS和小鼠黑色素瘤细胞B16F10，我们发现p37在体外增强细胞运动、迁移和侵袭。在C57BL/6小鼠的实验性转移模型中，p37腺病毒感染的B16F10细胞在肺中形成更多的转移病灶。此外，p37 促进表皮生长因子受体 (EGFR) 和细胞外信号调节激酶的磷酸化以及基质金属蛋白酶-2 (MMP-2) 的活性。 MMP 抑制剂显着阻断 p37 诱导的 EGFR，但对细胞外信号调节激酶磷酸化几乎没有影响，而 p37 诱导的 MMP-2 激活仅被 MEK1/2 抑制剂或 EGFR 抑制剂部分抑制。然而，所有这些抑制剂都显着降低了 p37 诱导的 AGS 细胞的侵袭性。这些结果表明p37可能通过增加MMP-2的活性来刺激侵袭，从而诱导EGFR磷酸化并促进猪鼻支原体感染时的肿瘤转移。 p37 及其调控分子可能成为癌症治疗的潜在靶点。
High Mycoplasma infection in gastric cancer tissues suggests a possible association between Mycoplasma infection and tumorigenesis. By using human gastric cancer cells AGS and mouse melanoma cells B16F10 stably expressing p37, the major immunogen of Mycoplasma hyorhinis, we found that p37 enhanced cell motility, migration, and invasion in vitro. With experimental metastasis model in C57BL/6 mice, p37 adenovirus-infected B16F10 cells formed more metastasis lesions in the lung. Furthermore, p37 promoted the phosphorylation of epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase and the activity of matrix metalloproteinase-2 (MMP-2). Inhibitor of MMPs significantly blocked p37-induced EGFR but has little effect on extracellular signal-regulated kinase phosphorylation, whereas the p37-induced MMP-2 activation was only partially suppressed by inhibitor of MEK1/2 or by inhibitor of EGFR. However, all these inhibitors significantly reduced the p37-induced invasiveness of AGS cells. These results suggest that p37 may stimulate invasion by increasing the activity of MMP-2, thereby inducing EGFR phosphorylation and contributing to tumor metastasis on M. hyorhinis infection. p37 and its regulated molecules could be the potential targets for cancer therapy.