Mesenchymal Stem/Stromal Cells under Stress Increase Osteosarcoma Migration and Apoptosis Resistance via Extracellular Vesicle Mediated Communication.
Mesenchymal Stem/Stromal Cells under Stress Increase Osteosarcoma Migration and Apoptosis Resistance via Extracellular Vesicle Mediated Communication.
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DOI：
10.1371/journal.pone.0166027
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Pochampally R
中科院分区：
文献类型：
--
作者：
Vallabhaneni KC;Hassler MY;Abraham A;Whitt J;Mo YY;Atfi A;Pochampally R
研究表明，骨髓间充质干/基质细胞（mesenchymal stem/stromal cells，MSCs）参与实体瘤的生长和转移，但在骨肉瘤（osteosarcoma，OS）中的作用机制尚不清楚。先前的研究已经提出了OS细胞可以通过以囊泡或非囊泡形式释放支持性大分子和生长因子来从肿瘤的营养缺乏核心中的相关MSC获得支持的可能性。在本研究中，我们使用应激间充质干细胞（SD-MSC），对照MSC和OS细胞来检查营养缺乏核心中的肿瘤相关MSC为附近的肿瘤细胞提供促增殖，抗凋亡和转移支持的假设。研究SD-MSC条件培养基的作用的测定显示，与仅在血清饥饿条件下生长的OS细胞相比，OS细胞保持增殖。此外，MSC和SD-MSC条件培养基中的OS细胞对凋亡具有显著抗性，并且在暴露于条件培养基或来自MSC和SD-MSC的EV的细胞中观察到伤口愈合率增加。与来自SD-MSC的细胞外囊泡（EV）孵育的OS细胞的RT-PCR测定揭示了微RNA，其可以潜在地靶向通过计算机算法预测的代谢和转移相关基因，包括单羧酸转运蛋白、骨形态发生受体2型、成纤维细胞生长因子7、基质金属蛋白酶-1和局灶性粘附激酶-1。黏着斑激酶STK 11的表达水平的变化通过定量PCR测定来证实。总之，这些数据表明MSC在骨肉瘤生长中的肿瘤支持作用，其与在模拟实体瘤的营养缺乏核心的条件下从MSC释放的EV的miRNA含量强烈相关。
Studies have shown that mesenchymal stem/stromal cells (MSCs) from bone marrow are involved in the growth and metastasis of solid tumors but the mechanism remains unclear in osteosarcoma (OS). Previous studies have raised the possibility that OS cells may receive support from associated MSCs in the nutrient deprived core of the tumors through the release of supportive macromolecules and growth factors either in vesicular or non-vesicular forms. In the present study, we used stressed mesenchymal stem cells (SD-MSCs), control MSCs and OS cells to examine the hypothesis that tumor-associated MSCs in nutrient deprived core provide pro-proliferative, anti-apoptotic, and metastatic support to nearby tumor cells. Assays to study of the effects of SD-MSC conditioned media revealed that OS cells maintained proliferation when compared to OS cells grown under serum-starved conditions alone. Furthermore, OS cells in MSCs and SD-MSC conditioned media were significantly resistant to apoptosis and an increased wound healing rate was observed in cells exposed to either conditioned media or EVs from MSCs and SD-MSCs. RT-PCR assays of OS cells incubated with extracellular vesicles (EVs) from SD-MSCs revealed microRNAs that could potentially target metabolism and metastasis associated genes as predicted by in silico algorithms, including monocarboxylate transporters, bone morphogenic receptor type 2, fibroblast growth factor 7, matrix metalloproteinase-1, and focal adhesion kinase-1. Changes in the expression levels of focal adhesion kinase, STK11 were confirmed by quantitative PCR assays. Together, these data indicate a tumor supportive role of MSCs in osteosarcoma growth that is strongly associated with the miRNA content of the EVs released from MSCs under conditions that mimic the nutrient deprived core of solid tumors.
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影响因子：
--
作者：
Ren K;Lu X;Yao N;Chen Y;Yang A;Chen H;Zhang J;Wu S;Shi X;Wang C;Sun X
通讯作者：
Sun X
影响因子：
3.7
作者：
Boisen MK;Dehlendorff C;Linnemann D;Nielsen BS;Larsen JS;Osterlind K;Nielsen SE;Tarpgaard LS;Qvortrup C;Pfeiffer P;Holländer NH;Keldsen N;Hansen TF;Jensen BB;Høgdall EV;Jensen BV;Johansen JS
通讯作者：
Johansen JS
miR-21诱导肌成纤维细胞分化并促进乳腺叶状肿瘤恶性进展
影响因子：
11.2
作者：
Gong, Chang;Nie, Yan;Liu, Qiang
通讯作者：
Liu, Qiang
影响因子：
56.9
作者：
Pillai, RS;Bhattacharyya, SN;Filipowicz, W
通讯作者：
Filipowicz, W
DOI：
10.1073/pnas.0804438105
发表时间：
2008-09-16
影响因子：
11.1
作者：
Li, Zhaoyong;Hassan, Mohammad Q.;Stein, Gary S.
通讯作者：
Stein, Gary S.