Endometriotic Epithelial Cell Response to Macrophage-Secreted Factors is Dependent on Extracellular Matrix Context.

Endometriotic Epithelial Cell Response to Macrophage-Secreted Factors is Dependent on Extracellular Matrix Context.
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子宫内膜细胞对巨噬细胞分泌因子的反应取决于细胞外基质环境。

DOI:
10.1007/s12195-014-0339-6
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发表时间:
2014-09
影响因子:
2.8
通讯作者:
Kreeger PK
Kreeger PK
中科院分区:
工程技术4区
文献类型:
--
作者:
Pollock K;Jaraczewski TJ;Carroll MJ;Lebovic DI;Kreeger PK

文献摘要

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子宫内膜异位症是一种慢性疾病,在异位病变中发现类似于在位子宫内膜的上皮细胞和基质细胞。为了研究微环境因素如细胞外基质和巨噬细胞如何影响疾病进展,将12 Z(永生化异位上皮细胞系)在组织培养塑料(TCP)上或在重组基底膜(rBM)或胶原I的凝胶中培养。与其他条件下的细胞不同,rBM中的细胞以67 kDa非整合素层粘连蛋白受体(67 LR)依赖性方式形成多细胞结构。为了检查巨噬细胞分泌的因子对细胞行为的影响,用来自分化的THP-1(永生化单核细胞系)的条件培养基处理所有三种基质上的12 Z细胞。仅在rBM中培养的细胞中观察到显著的增殖和侵袭,表明细胞外基质线索有助于决定细胞对可溶性信号的反应。然后用条件培养基中检测到的单个细胞因子处理在rBM上培养的细胞,在暴露于白细胞介素-8(CXCL 8/IL-8)后观察到增殖增加,并且在用肝素结合EGF样生长因子(HB-EGF)处理后观察到增殖和侵袭增加。这项研究表明,rBM凝胶可用于诱导体外病变的形成,以确定影响增殖和侵袭的可溶性因子。
Endometriosis is a chronic disease in which epithelial and stromal cells that resemble the eutopic endometrium are found in ectopic lesions. In order to examine how microenvironmental factors such as extracellular matrix and macrophages influence disease progression, 12Z (an immortalized ectopic epithelial cell line) were cultured on tissue culture plastic (TCP) or in gels of recombinant basement membrane (rBM) or collagen I. Unlike cells in other conditions, cells in rBM formed multi-cellular structures in a 67 kDa non-integrin laminin receptor (67LR)-dependent manner. To examine the impact of macrophage-secreted factors on cell behavior, 12Z cells on all three substrates were treated with conditioned media from differentiated THP-1 (an immortalized monocytic cell line). Significant proliferation and invasion was observed only with cells cultured in rBM, indicating that extracellular matrix cues help dictate cell response to soluble signals. Cells cultured on rBM were then treated with individual cytokines detected in the conditioned media, with increased proliferation observed following exposure to interleukin-8 (CXCL8/IL-8) and both increased proliferation and invasion following treatment with heparin-binding EGF-like growth factor (HB-EGF). This study suggests that rBM gels can be used to induce in vitro lesion formation in order to identify soluble factors that influence proliferation and invasion.