Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8

Journal of Experimental & Clinical Cancer Research

Huiyi Wu¹  Juan Huo¹  Ping Zheng¹  Shaolin Zhao¹  Ting Zhang¹  Huanhuan Zhang¹  Xu Zhang³  Jin Yang¹  Ying Zhou¹  Wei Li² 

[1] Center of Research Laboratory, The First People’s Hospital of Lianyungang, 182 Tongguan Road, Lianyungang 222001, China;Department of Pathology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, China;School of Medical Science and Laboratory Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, China

关键词: Angiogenesis;    Migration;    Proliferation;    Interleukin-8;    Gastric cancer;    Mesenchymal stem cells;   

Others  :  1220696
DOI  :  10.1186/s13046-015-0172-3

 received in 2015-02-02, accepted in 2015-05-08,  发布年份 2015

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusion

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.

【 授权许可】

   
2015 Li et al.; licensee BioMed Central.

【 图 表 】

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