Expression of interleukin (IL)-11 and IL-11 receptor in human colorectal adenocarcinoma: IL-11 up-regulation of the invasive and proliferative activity of human colorectal carcinoma cells.
Expression of interleukin (IL)-11 and IL-11 receptor in human colorectal adenocarcinoma: IL-11 up-regulation of the invasive and proliferative activity of human colorectal carcinoma cells.
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DOI：
10.3892/ijo.29.4.869
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发表时间：
2006-10
影响因子：
5.2
通讯作者：
A. Yoshizaki;T. Nakayama;K. Yamazumi;Y. Yakata;Mitsuru Taba;I. Sekine
中科院分区：
文献类型：
--
作者：
A. Yoshizaki;T. Nakayama;K. Yamazumi;Y. Yakata;Mitsuru Taba;I. Sekine
先前的研究表明，白细胞介素 (IL)-11/IL-11 受体 α 链 (IL-11Ralpha) 是 PI3K、MAPK 和 JAK-STAT 激活细胞因子/受体家族的成员，与肿瘤进展的调节相关。在本研究中，我们建立了人结直肠腺癌（CRC）中IL-11/IL-11Rα的表达谱，并阐明了其信号通路及其在CRC细胞系侵袭活性中的作用。为了阐明IL-11/IL-11Rα的作用，我们通过免疫组织化学检查了103例CRC和24例结直肠腺瘤。此外，我们研究了CRC细胞系的细胞信号通路的侵袭活性。 IL-11Rα表达与肿瘤侵袭和淋巴浸润相关（分别p<0.01）。重组人IL-11（rhIL-11）促进HT-29细胞的迁移和增殖，并激活PI3K和p44/p42 MAPK通路。 PI3K 抑制剂 Wortmannin 和 p44/p42 MAPK 抑制剂 PD98059 分别显着降低 rhIL-11 对侵袭和增殖活性的促进作用。总之，IL-11Rα表达与CRC细胞的临床病理特征相关，IL-11通过PI3K促进侵袭，并通过p44/p42 MAPK上调CRC细胞的增殖。这些发现表明IL-11/IL-11R通路在CRC的进展中发挥重要作用。
Previous investigations have shown that interleukin (IL)-11/IL-11 receptor alpha-chain (IL-11Ralpha), a member of the PI3K, MAPK and JAK-STAT activating family of cytokines/receptors, correlates with the regulation of tumor progression. In this study, we established the IL-11/IL-11Ralpha expression profile in human colorectal adenocarcinoma (CRC) and clarified its signaling pathway and role in the invasion activity of CRC cell lines. To elucidate the role of IL-11/IL-11Ralpha, we examined 103 cases of CRC and 24 cases of colorectal adenoma by immunohistochemistry. In addition, we investigated the invasive activity of cell signaling pathway of CRC cell lines. The IL-11Ralpha expression was correlated with tumor invasion and lymphatic infiltration (p<0.01, respectively). Recombinant human IL-11 (rhIL-11) promoted the migration and proliferation of HT-29 cells and activated the PI3K and p44/p42 MAPK pathways. Wortmannin, a PI3K inhibitor, and PD98059, a p44/p42 MAPK inhibitor, significantly reduced the promotion of invasion and proliferation activity by rhIL-11, respectively. In summary, the IL-11Ralpha expression was correlated with clinicopathological features and IL-11 promoted the invasion via the PI3K and up-regulated the proliferation via the p44/p42 MAPK in CRC cells. These findings suggested that the IL-11/IL-11R pathway plays an important role in the progression of CRC.