Targeting regulation of the tumour microenvironment induces apoptosis of breast cancer cells by an affinity hemoperfusion adsorbent
Targeting regulation of the tumour microenvironment induces apoptosis of breast cancer cells by an affinity hemoperfusion adsorbent
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亲和血液灌流吸附剂靶向调控肿瘤微环境诱导乳腺癌细胞凋亡
DOI：
10.1080/21691401.2021.1902337
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Lailiang Ou
中科院分区：
文献类型：
--
作者：
Lichun Wang;Jian Chen;Yamin Chai;Wenyan Han;Jie Shen;Nan Li;Jinyan Lu;Yunzheng Du;Zhuang Liu;Yameng Yu;Jingzhe Dong;Lailiang Ou
肿瘤微环境细胞因子网络（tumor microenvironment， TME）在肿瘤的生长和发展中起着重要作用。目前的工作旨在提供一种基于靶向调节TME细胞因子的癌症治疗新策略。本研究中，肝素偶联聚乙烯醇（PVA-H）微球作为吸附剂被开发用于选择性去除肿瘤诱导的免疫抑制细胞因子，如血管内皮生长因子（VEGF）和转化生长因子-β (TGF-β)，但不能去除具有免疫刺激作用和抑制肿瘤生长的肿瘤坏死因子-α (TNF-α)。采用细胞活力法、流式细胞术和mRNA芯片法检测灌注后乳腺癌细胞的增殖和凋亡情况。结果表明，PVA-H微球对VEGF（74.39%）和TGF-β(86.39%)的吸收率较高，对TNF-α的吸收率较低（4.16%）。这些细胞因子的调控对乳腺癌细胞具有显著的抗增殖和促凋亡作用，这从mRNA表达水平的变化中得到进一步证实。因此，通过选择性地消耗免疫抑制细胞因子的亲和力吸附剂靶向TME内的调节途径可能是一种新的有前途的癌症治疗策略。
The cytokine network of tumor microenvironment (TME) plays an important role in cancer growth and progression. The current work aims to provide a new strategy for cancer therapy based on targeted regulation of cytokines in the TME. Here, heparin-coupled polyvinyl alcohol (PVA-H) microspheres have been developed as an adsorbent for selectively remove tumor-induced immunosuppressive cytokines, such as vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β), but not tumor necrosis factor-alpha (TNF-α) which has an immune-stimulating effect and can inhibit tumor growth. The proliferation and apoptosis of breast cancer cells after perfusion were tested by cell viability assays, flow cytometry analysis and mRNA microarray assays. Results showed that the PVA-H microspheres efficiently absorbed the majority of VEGF (74.39%) and TGF-β (86.39%), but much less TNF-α (4.16%). The regulation of the cytokines had remarkable anti-proliferative and pro-apoptotic effects on breast cancer cells, which was further confirmed from the change of mRNA expression levels. Thus, targeting regulatory pathways within the TME by an affinity adsorbent that selectively deplete immunosuppressive cytokines is potentially a new and promising strategy for cancer therapy.
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DOI：
10.1023/b:jomg.0000037157.94207.33
发表时间：
2004-04-01
影响因子：
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作者：
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