Impact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferation
Impact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferation
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DOI：
10.1016/j.bbrc.2013.05.013
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发表时间：
2013-06-14
影响因子：
3.1
通讯作者：
Dwyer, Roisin M.
中科院分区：
文献类型：
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作者：
Hogan, Niamh M.;Joyce, Myles R.;Dwyer, Roisin M.
众所周知，间充质干细胞可以植入并整合到结直肠肿瘤的结构中，但人们对其植入后的命运知之甚少。本研究旨在研究间充质干细胞（MSC）和结肠癌细胞（CCC）相互作用的介质。间充质干细胞和结肠癌细胞（HT29 和 HCT-116）在 3 维支架上单独培养或共培养。在第 1、3 和 7 天收获含有所有分泌因子的条件培养基。通过 Chemi-array、ELISA（巨噬细胞迁移抑制因子 (MIF)、纤溶酶原激活剂抑制剂 1 型 (PAI-1)）和 RQ-PCR 分析趋化因子的分泌和表达。分别使用 Transwell 插入片段和 MTS 增殖测定分析结肠癌细胞对重组 PAI-1、MSC 和 MSCs + PAI-1 抗体的迁移和增殖反应。化学阵列显示每个细胞群分泌多种因子，包括 PAI-1 和 MIF。 ELISA 分析显示间充质干细胞分泌最高水平的 PAI-1（MSC 平均 10.6 ng/mL，CCC 平均 1.01 ng/mL），而结肠癌细胞是 MIF 的主要来源。 MSC 分泌的 PAI-1 刺激了两种 CCC 系的显着迁移，趋化因子抗体显示可以阻断这种效应（阻断 67-88%）。间充质干细胞分泌的 PAI-1 对 CCC 增殖具有细胞系依赖性效应，HCT-116 细胞在所有浓度下均显示增殖减少，而 HT29 细胞在 PAI-1 水平较高的情况下显示增殖增加。这是第一项确定 PAI-1 作为间充质干细胞/结肠癌细胞相互作用的重要介质的研究，并强调了间充质干细胞分泌的 PAI-1 对结肠的显着功能影响癌细胞。 (C) 2013 Elsevier Inc. 保留所有权利。
Mesenchymal Stem Cells are known to engraft and integrate into the architecture of colorectal tumours, with little known regarding their fate following engraftment. This study aimed to investigate mediators of Mesenchymal Stem Cell (MSC) and colon cancer cell (CCC) interactions. Mesenchymal Stem Cells and colon cancer cells (HT29 and HCT-116) were cultured individually or in co-culture on 3-dimensional scaffolds. Conditioned media containing all secreted factors was harvested at day 1, 3 and 7. Chemokine secretion and expression were analyzed by Chemi-array, ELISA (Macrophage migration inhibitory factor (MIF), plasminogen activator inhibitor type 1 (PAI-1)) and RQ-PCR. Colon cancer cell migration and proliferation in response to recombinant PAI-1, MSCs and MSCs + antibody to PAI-1 was analyzed using Transwell inserts and an MTS proliferation assay respectively.Chemi-array revealed secretion of a wide range of factors by each cell population, including PAI-1 and MIF. ELISA analysis revealed Mesenchymal Stem Cells to secrete the highest levels of PAI-1 (MSC mean 10.6 ng/mL, CCC mean 1.01 ng/mL), while colon cancer cells were the principal source of MIF. MSC-secreted PAI-1 stimulated significant migration of both CCC lines, with an antibody to the chemokine shown to block this effect (67-88% blocking,). A cell-line dependant effect on CCC proliferation was shown for Mesenchymal Stem Cell-secreted PAI-1 with HCT-116 cells showing decreased proliferation at all concentrations, and HT29 cells showing increased proliferation in the presence of higher PAI-1 levels.This is the first study to identify PAI-1 as an important mediator of Mesenchymal Stem Cell/colon cancer cell interactions and highlights the significant functional impact of Mesenchymal Stem Cell-secreted PAI-1 on colon cancer cells. (C) 2013 Elsevier Inc. All rights reserved.