Adipokine regulation of colon cancer: adiponectin attenuates interleukin-6-induced colon carcinoma cell proliferation via STAT-3.
Adipokine regulation of colon cancer: adiponectin attenuates interleukin-6-induced colon carcinoma cell proliferation via STAT-3.
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DOI：
10.1002/mc.20644
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发表时间：
2010-07
影响因子：
4.6
通讯作者：
Birmingham, Janette M.
中科院分区：
文献类型：
--
作者：
Fenton, Jenifer I.;Birmingham, Janette M.
肥胖导致与结肠癌风险相关的特定脂肪因子循环水平升高。疾病状态与瘦素、胰岛素、IGF-1和IL-6升高有关。相反，肥胖个体的脂联素水平会降低。先前，我们证明了脂肪因子增强肿瘤前细胞增殖，而不是正常的结肠上皮细胞，在体外证明了脂肪因子对结肠癌进展的不同影响。我们采用晚期肝癌细胞模型，即小鼠MC-38结肠癌细胞，比较肥胖相关脂肪因子（瘦素、胰岛素、IGF-1和IL-6）对MC-38细胞增殖的影响，并确定脂联素（全长或球状）是否可以调节脂肪因子诱导的细胞增殖。我们发现胰岛素和IL-6，而不是瘦素和IGF-1，可以诱导MC-38细胞的增殖。脂联素处理的MC-38细胞不抑制胰岛素诱导的细胞增殖，但通过降低STAT-3的磷酸化和活化，抑制il -6诱导的细胞增殖。IL-6使MC-38细胞一氧化氮（NO）生成增加；与脂联素共处理可阻断IL-6诱导的iNOS和随后的NO生成。这些数据与我们实验室先前报道的使用YAMC（模型正常结肠上皮细胞）和IMCE（模型肿瘤前细胞）细胞的结果进行了比较。这些细胞系被用来构建一个模型，总结肥胖的激素后果，以及结肠上皮细胞在癌变过程中对差异调节的影响。这些数据综合起来，突出了肥胖相关癌症的机制，并可能导致潜在的靶向治疗。
Obesity results in increased circulating levels of specific adipokines which are associated with colon cancer risk. The disease state is associated with increased leptin, insulin, IGF-1, and IL-6. Conversely, adiponectin levels are decreased in obese individuals. Previously, we demonstrated adipokine-enhanced cell proliferation in preneoplastic, but not normal, colon epithelial cells, demonstrating a differential effect of adipokines on colon cancer progression in vitro. Using a model of late stage carcinoma cancer cell, namely murine MC-38 colon carcinoma cells, we compared the effect of obesity-associated adipokines (leptin, insulin and IGF-1 and IL-6) on MC-38 cell proliferation and determined whether adiponectin (full length or globular) could modulate adipokine-induced cell proliferation. We show that insulin and IL-6, but not leptin and IGF-1, induce proliferation in MC-38 cells. Adiponectin treatment of MC-38 cells did not inhibit insulin-induced cell proliferation but did inhibit IL-6-induced cell proliferation by decreasing STAT-3 phosphorylation and activation. Nitric oxide (NO) production was increased in MC-38 cells treated with IL-6; co-treatment with adiponectin blocked IL-6 induced iNOS and subsequent NO production. These data are compared to previously reported findings from our laboratory using the YAMC (model normal colon epithelial cells) and IMCE (model preneoplastic) cells. The cell lines are utilized to construct a model summarizing the hormonal consequences of obesity and the impact on the differential regulation of colon epithelial cells along the continuum to carcinoma. These data, taken together, highlight mechanisms involved in obesity-associated cancers and may lead to potential targeted therapies.
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影响因子：
50.3
作者：
Bromberg J;Wang TC
通讯作者：
Wang TC
影响因子：
29.4
作者：
Fayad, Raja;Pini, Maria;Fantuzzi, Giamila
通讯作者：
Fantuzzi, Giamila
影响因子：
11
作者：
Huang, SP;Wu, MS;Lin, JT
通讯作者：
Lin, JT
影响因子：
4.1
作者：
Ogunwobi, Olorunseun O.;Beales, Ian L. P.
通讯作者：
Beales, Ian L. P.
影响因子：
50.3
作者：
Bollrath, Julia;Phesse, Toby J.;Greten, Florian R.
通讯作者：
Greten, Florian R.