Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8.
Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8.
复制标题
胃癌来源的间充质干细胞通过分泌白细胞介素8促进胃癌进展。
DOI：
10.1186/s13046-015-0172-3
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发表时间：
2015-05-20
期刊：
影响因子：
--
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Li W;Zhou Y;Yang J;Zhang X;Zhang H;Zhang T;Zhao S;Zheng P;Huo J;Wu H
骨髓间充质干细胞（BM-MSCs）与肿瘤的生长和进展密切相关。然而，肿瘤驻留MSC在癌症中的作用尚未完全阐明。本研究旨在探讨胃癌源性间充质干细胞（GC-MSCs）对胃癌的调控作用及其机制。GC-MSC从原发性人胃癌组织中分离并表征。MTT法和集落形成实验检测GC-MSCs对胃癌细胞增殖的影响。Transwell迁移实验检测GC-MSCs对胃癌细胞迁移的影响。通过RT-PCR和Luminex法检测胃癌细胞与GC-MSCs共培养体系中促血管生成因子的表达和分泌，分析GC-MSCs与胃癌细胞相互作用对GC-MSCs促血管生成能力的调节作用。试管形成试验用于进一步验证胃癌细胞或GC-MSCs的血管生成能力。用Luminex法筛选GC-MSCs培养上清中的细胞因子谱，并用中和抗体鉴定关键的有效细胞因子。Western blot检测胃癌细胞Akt和Erk 1/2的活化。GC-MSC对BGC-823和MKN-28细胞的增殖和迁移有促进作用，其作用强于癌旁组织来源的MSC（GCN-MSC）和骨髓来源的MSC（BM-MSC）。GC-MSCs中促血管生成因子的表达水平高于GCN-MSCs和BM-MSCs。在10 % GC-MSC-CM处理后，BGC-823和MKN-28细胞表达增加的促血管生成因子水平，并且比单独的癌细胞更有效地促进管形成。此外，GC-MSCs产生的白细胞介素-8（IL-8）水平比GCN-MSCs或BM-MSCs高得多。通过中和抗体阻断IL-8显著减弱GC-MSCs的促肿瘤作用。另外，10%CM的IL-8分泌的GC-MSC诱导BGC-823和MKN-28细胞中Akt或Erk 1/2通路的激活。肿瘤驻留GC-MSCs通过分泌IL-8促进胃癌的生长和进展，其作用优于GCN-MSCs和BM-MSCs，有望成为胃癌治疗的靶点。
Bone marrow mesenchymal stem cells (BM-MSCs) have been identified to be closely associated with tumor growth and progression. However, the roles of tumor-resident MSCs in cancer have not been thoroughly clarified. This study was to investigate the regulating effect of gastric cancer-derived MSCs (GC-MSCs) on gastric cancer and elucidate the underlying mechanism. GC-MSCs were isolated from primary human gastric cancer tissues and characterized. The effect of GC-MSCs on gastric cancer cell proliferation was analyzed by MTT assay and colony formation assay. Transwell migration assay was performed to evaluate the influence of GC-MSCs in gastric cancer cell migration. The regulating effects of interactions between gastric cancer cells and GC-MSCs on their pro-angiogenic abilities were analyzed in a co-culture system, with the expression, and secretion of pro-angiogenic factors detected by RT-PCR and Luminex assay. Tube formation assay was used to further validate the angiogenic capability of gastric cancer cells or GC-MSCs. Cytokine profiles in the supernatant of GC-MSCs were screened by Luminex assay and neutralizing antibody was used to identify the key effective cytokines. The activations of Akt and Erk1/2 in gastric caner cells were detected by Western blot. GC-MSC treatment enhanced the proliferation and migration of BGC-823 and MKN-28 cells, which was more potently than MSCs from adjacent non-cancerous tissues (GCN-MSCs) or bone marrow (BM-MSCs). Higher expression levels of pro-angiogenic factors were detected in GC-MSCs than GCN-MSCs or BM-MSCs. After 10 % GC-MSC-CM treatment, BGC-823, and MKN-28 cells expressed increased levels of pro-angiogenic factors and facilitated tube formation more potently than cancer cells alone. Furthermore, GC-MSCs produced an extremely higher level of interleukin-8 (IL-8) than GCN-MSCs or BM-MSCs. Blockade of IL-8 by neutralizing antibody significantly attenuated the tumor-promoting effect of GC-MSCs. In addition, 10 % CM of IL-8-secreted GC-MSCs induced the activations of Akt or Erk1/2 pathway in BGC-823 and MKN-28 cells. Tumor-resident GC-MSCs promote gastric cancer growth and progression more efficiently than GCN-MSCs or BM-MSCs through a considerable secretion of IL-8, which could be a possible target for gastric cancer therapy.
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82.9
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作者：
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