Interleukin‐8 modulates growth and invasiveness of estrogen receptor‐negative breast cancer cells
Interleukin‐8 modulates growth and invasiveness of estrogen receptor‐negative breast cancer cells
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DOI：
10.1002/ijc.22930
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发表时间：
2007-11
影响因子：
6.4
通讯作者：
C. Yao;Ying Lin;M. Chua;C. Ye;J. Bi;Wen Li;Yi-fan Zhu;Shenming Wang
中科院分区：
文献类型：
--
作者：
C. Yao;Ying Lin;M. Chua;C. Ye;J. Bi;Wen Li;Yi-fan Zhu;Shenming Wang
尽管手术和辅助疗法取得了重大进展，但乳腺癌，尤其是雌激素受体（ER）阴性乳腺癌，仍然很难治疗。ER的缺失与肿瘤的进展、复发、转移和预后不良有关。在生物学特征的其他差异中，ER阴性乳腺癌表达高水平的白细胞介素-8（IL-8），而ER阳性乳腺癌则不表达。IL-8是一种多功能细胞因子，在肿瘤的形成和发展中具有许多重要的生物学功能。我们的目的是通过使用RNA干扰来特异性敲低ER阴性乳腺癌细胞系MDA-MB-231和MDA-MB-468中IL-8的表达，研究IL-8在ER阴性乳腺癌进展中的作用。在体外，IL-8的抑制导致细胞侵袭的显著降低（p < 0.001），但对细胞增殖或细胞周期没有影响。在体内，IL-8的抑制显著降低了微血管密度（p < 0.05），并显著减少了中性粒细胞浸润到肿瘤中（p < 0.05）。与体外观察结果相反，抑制IL-8促进了裸鼠中的肿瘤生长（p < 0.05）。我们的研究结果表明，IL-8在调节ER阴性乳腺癌进展中的复杂作用可能部分与其对中性粒细胞的强效趋化作用有关，而中性粒细胞又介导了IL-8的许多生物学功能。© 2007 Wiley利斯公司
Breast cancer, especially estrogen receptor (ER)‐negative breast cancer, remains hard to treat despite major advances in surgery and adjuvant therapies. The deletion of ER has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis. Among other differences in biological features, ER‐negative breast cancers express high levels of interleukin‐8 (IL‐8), whereas their ER‐positive counterparts do not. IL‐8 is a multi‐functional cytokine with many important biological functions in tumor formation and development. We aimed to study the role(s) of IL‐8 in ER‐negative breast cancer progression by using RNA interference to specifically knockdown IL‐8 expression in ER‐negative breast cancer cell lines MDA‐MB‐231 and MDA‐MB‐468. In vitro, suppression of IL‐8 led to significant reductions in cell invasion (p < 0.001), but had no effects on cell proliferation or cell cycle. In vivo, suppression of IL‐8 significantly reduced the microvessel density (p < 0.05), and markedly reduced neutrophil infiltration into the tumors (p < 0.05). In contrast to in vitro observations, suppression of IL‐8 promoted tumor growth in nude mice (p < 0.05). Our results imply that the complex roles of IL‐8 in the regulation of ER‐negative breast cancer progression may in part be related to its potent chemotactic effects on neutrophils, which in turn mediates many of the biological functions of IL‐8. © 2007 Wiley‐Liss, Inc.