Uterine smooth muscle cells increase invasive ability of endometrial carcinoma cells through tumor-stromal interaction
Uterine smooth muscle cells increase invasive ability of endometrial carcinoma cells through tumor-stromal interaction
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DOI：
10.1007/s10585-007-9079-5
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发表时间：
2007-10-01
影响因子：
4
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
--
作者：
Tsukamoto, Hirohisa;Shibata, Kiyosumi;Kikkawa, Fumitaka
子宫内膜癌（EMCA）淋巴结转移的发生率随着肌层浸润深度的增加而增加，并且已发现浸润深度对预后有重大影响。在本研究中，我们评估了肿瘤间质相互作用对EMCA细胞侵袭行为的影响，并检测了SDF-1 α/CXCL 12-CXCR 4在EMCA细胞和子宫平滑肌细胞（UtSMCs）相互作用中的作用。我们使用5种人EMCA细胞系如AMEC和RL 95细胞研究了UtSMCs产生和分泌的SDF-1 α/CXCL 12是否诱导EMCA细胞迁移。UTSMC条件培养基（CM）中SDF-1 α/CXCL 12浓度为4，120 +/- 530 pg/ml。用CM处理UtSMCs和接种的UtSMCs显著诱导AMEC和RL 95细胞迁移。CXCR 4 mAb（12 G5）和CXCR 4拮抗剂（AMD 3100）预处理可显著抑制诱导的细胞迁移。UtSMCs CM对AMEC和RL 95细胞的处理以时间依赖性方式刺激Akt磷酸化。用磷脂酰肌醇3激酶抑制剂渥曼青霉素预处理AMEC和RL 95细胞可显著抑制CM诱导的UtSMCs细胞迁移。UtSMCs和EMCA之间的SDF-1 α/CXCL 12-CXCR 4趋化因子轴通过激活PI 3 K-Akt信号通路在子宫内膜癌肌层浸润中发挥重要作用。抑制这一途径可能是治疗早期子宫体癌的有效靶点。
The incidence of lymph node metastasis by endometrial carcinoma (EMCA) increases with the depth of myometrial invasion, and this depth of invasion has been found to have a major impact on the outcome. In the present study, we assessed the effect of tumor-stromal interactions on the invasive behavior of EMCA cells and examined the involvement of SDF-1alpha/CXCL12-CXCR4 in the interaction of EMCA cells and uterine smooth muscle cells (UtSMCs). We investigated whether SDF-1alpha/CXCL12 produced and secreted from UtSMCs induces EMCA cell migration by using 5 human EMCA cell lines such as AMEC and RL95 cells. The SDF-1alpha/CXCL12 concentration in conditioned medium (CM) of UtSMCs(was 4,120 +/- 530 pg/ml. Treatments with CM of UtSMCs and plated UtSMCs significantly induced both AMEC and RL95 cell migration. The induced cell migrations were significantly inhibited by CXCR4 mAb (12G5) and CXCR4 antagonist (AMD3100) pre-treatments. Treatments with UtSMCs CM to AMEC and RL95 cells stimulated Akt phosphorylation in a time-dependent manner. Pre-treatment of AMEC and RL95 cells with wortmannin as a PI3K inhibitor significantly inhibited UtSMCs CM-induced cell migration. The SDF-1alpha/CXCL12-CXCR4 chemokine axis between UtSMCs and EMCA played an important role in the muscular infiltration of endometrial cancer through activation of PI3K-Akt signaling pathway. Suppression of this pathway could be an effective target for the treatment of early uterine body cancer in particular.