Departamento de Biomedicina Molecular, CINVESTAV-IPN, Apartado, México, D.F., México.
Arch Med Res. 2010 Apr;41(3):170-81. doi: 10.1016/j.arcmed.2010.04.010.
Interleukin 1 beta (IL-1beta) and other inflammatory cytokines are reported to induce phenotypic changes in epithelial breast cancer tumor cells related to increased invasiveness. Mechanisms involved in the process are not well understood.
The noninvasive breast cancer epithelial cell line MCF-7 was used to investigate the IL-1beta-induced phenotype. Live cells expressing EGFP-actin were monitored for cell morphology changes and actin cytoskeleton dynamics by time-lapse video microscopy in the presence of IL-1beta and specific inhibitors of actin signaling pathways. Chemotaxis, invasion of Matrigel, MMP activity and expression of S100A4 in cells treated with IL-1beta were assessed by migration assays, zymograms and immunoblots.
Exposure to IL-1beta specifically induced a change in MCF-7 cells from a typical epithelial morphology into elongated cells, showing numerous dynamic actin-rich lamellae and peripheral ruffles characteristic of fibroblasts. These cells could scatter from compact cell colonies and respond to chemoattractants such as the homing-associated chemokine CXCL-12. Pharmacological blockage of actin signaling pathways and negative mutants of RhoGTPases revealed that actin reorganization and enhanced motility are regulated via PI3K/Rac 1 activation. IL-1beta-stimulated cells expressed the metastasis promoter S100A4, increased secretion of active MMP-9 and MMP-2 and invasion of extracellular matrix proteins.
IL-1beta induces a PI3K/Rac 1-regulated reorganization of the actin cytoskeleton of MCF-7 cells that is required for cell scattering, elongation and migration. The enhanced motility is accompanied by expression of protein markers correlated with invasive behavior.
白细胞介素 1β（IL-1β）和其他炎症细胞因子据报道可诱导上皮性乳腺癌肿瘤细胞表型发生变化，与侵袭性增加有关。该过程涉及的机制尚不清楚。
使用非侵袭性乳腺癌上皮细胞系 MCF-7 来研究 IL-1β 诱导的表型。通过在存在 IL-1β和肌动蛋白信号通路的特定抑制剂的情况下，使用延时视频显微镜监测表达 EGFP-肌动蛋白的活细胞的细胞形态变化和肌动蛋白细胞骨架动力学。通过迁移测定、凝胶电泳和免疫印迹评估用 IL-1β 处理的细胞的趋化性、Matrigel 侵袭、MMP 活性和 S100A4 的表达。
暴露于 IL-1β 可特异性诱导 MCF-7 细胞从典型的上皮形态转变为长形细胞，表现出许多动态富含肌动蛋白的薄片和纤维母细胞特有的周边皱褶。这些细胞可以从紧密的细胞集落中分散出来，并对趋化剂（如归巢相关趋化因子 CXCL-12）做出反应。肌动蛋白信号通路的药理学阻断和 RhoGTPases 的负突变体表明，肌动蛋白重排和增强的运动性通过 PI3K/Rac 1 的激活来调节。IL-1β 刺激的细胞表达转移促进因子 S100A4，增加活性 MMP-9 和 MMP-2 的分泌以及细胞外基质蛋白的侵袭。
IL-1β 诱导 MCF-7 细胞的 PI3K/Rac 1 调节的肌动蛋白细胞骨架重排，这是细胞分散、伸长和迁移所必需的。增强的运动性伴随着与侵袭行为相关的蛋白标志物的表达。
