Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties.

Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties.
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DOI:
10.1016/j.biocel.2013.11.015
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发表时间:
2014-01
影响因子:
4
通讯作者:
El-Shinawi, Mohamed
El-Shinawi, Mohamed
中科院分区:
生物学2区
文献类型:
--
作者:
Mohamed, Mona M.;El-Ghonaimy, Eslam A.;Nouh, Mohamed A.;Schneider, Robert J.;Sloane, Bonnie F.;El-Shinawi, Mohamed

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虽然有越来越多的文献描述了巨噬细胞在乳腺癌中的作用,但巨噬细胞在炎性乳腺癌(IBC)中的作用尚不清楚。本研究的目的是分离和表征IBC和非IBC患者的肿瘤相关巨噬细胞,并确定它们在IBC中的作用。使用特异性单克隆抗体,通过免疫组织化学染色测量肿瘤浸润单核细胞/巨噬细胞(CD 14+和CD 68+)。在乳腺癌手术期间收集从腋静脉分支引流的血液,并通过流式细胞术分析评估总分离的白细胞中CD 14+的百分比。通过免疫磁珠技术从总白细胞中分离CD 14+细胞并培养过夜。收集由CD 14+调节的培养基,并使用细胞因子抗体阵列进行细胞因子谱分析。伤口愈合和侵袭测定用于测试由肿瘤引流的巨噬细胞高度分泌的细胞因子是否诱导乳腺癌细胞的运动和侵袭。我们发现巨噬细胞高度浸润于IBC患者的癌组织中。此外,与从非IBC患者收集的血液相比,从IBC患者的腋窝支流收集的血液高度富集有CD 14+细胞。从IBC患者分离的CD 14+细胞的细胞因子谱显示,与从非IBC患者分离的CD 14+细胞相比,肿瘤坏死因子-α、单核细胞趋化蛋白-1/CC-趋化因子配体2、白细胞介素-8和白细胞介素-10的分泌显著增加。肿瘤坏死因子-α、白细胞介素-8和白细胞介素-10在体外可显著增加IBC细胞的运动和侵袭能力。总之,从IBC患者的肿瘤微环境中分离的巨噬细胞分泌趋化性细胞因子,其可能增加IBC癌细胞的传播和转移。
Although there is a growing literature describing the role of macrophages in breast cancer, the role of macrophages in inflammatory breast cancer (IBC) is unclear. The aim of present study was to isolate and characterize tumor associated macrophages of IBC and non-IBC patients and define their role in IBC. Tumor infiltrating monocytes/macrophages (CD14+ and CD68+) were measured by immunohistochem-istry using specific monoclonal antibodies. Blood drained from axillary vein tributaries was collected during breast cancer surgery and the percentage of CD14+ in the total isolated leukocytes was assessed by flow cytometric analysis. CD14+ cells were separated from total leukocytes by immuno-magnetic beads technique and were cultured overnight. Media conditioned by CD14+ were collected and subjected to cytokine profiling using cytokine antibody array. Wound healing and invasion assays were used to test whether cytokines highly secreted by tumor drained macrophages induce motility and invasion of breast cancer cells. We found that macrophages highly infiltrate into carcinoma tissues of IBC patients. In addition blood collected from axillary tributaries of IBC patients is highly enriched with CD14+ cells as compared to blood collected from non-IBC patients. Cytokine profiling of CD14+ cells isolated from IBC patients revealed a significant increase in secretion of tumor necrosis factor-α; monocyte chemoat-tractant protein-1/CC-chemokine ligand 2; interleukin-8 and interleukin-10 as compared to CD14+ cells isolated from non-IBC patients. Tumor necrosis factor-a, interleukin-8 and interleukin-10 significantly increased motility and invasion of IBC cells in vitro. In conclusion, macrophages isolated from the tumor microenvironment of IBC patients secrete chemotactic cytokines that may augment dissemination and metastasis of IBC carcinoma cells.
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DOI: 10.1371/journal.pone.0055755
发表时间: 2013
期刊: PloS one
影响因子: 3.7
作者:
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