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YAP signaling in gastric cancer-derived mesenchymal stem cells is critical for its promoting role in cancer progression.

ABSTRACT: Cancer-associated mesenchymal stem cells (MSCs) are critically involved in tumor development and progression. However, the mechanisms of action for MSCs in cancer remain largely unknown. Herein, we reported that the expression of Yes-associated protein 1 (YAP) was higher in gastric cancer derived mesenchymal stem cells (GC?MSCs) than that in bone marrow derived MSCs (BM?MSCs). YAP knockdown not only inhibited the growth, migration and invasion, and stemness of GC?MSCs, but also suppressed their promoting effect on gastric cancer growth in vitro and in vivo. In addition, the interference of YAP expression in GC?MSCs also attenuated the promoting role of gastric cancer cells in endothelial cell tube formation and migration. Mechanistically, YAP knockdown reduced the activation of ?-catenin and its target genes in gastric cancer cells by GC?MSCs. Taken together, these findings suggest that YAP activation in GC?MSCs plays an important role in promoting gastric cancer progression, which may represent a potential target for gastric cancer therapy.

SUBMITTER: Pan Z

PROVIDER: S-EPMC5592864 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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YAP signaling in gastric cancer-derived mesenchymal stem cells is critical for its promoting role in cancer progression.

Pan Zhaoji Z Tian Yiqing Y Zhang Bin B Zhang Xu X Shi Hui H Liang Zhaofeng Z Wu Peipei P Li Rong R You Benshuai B Yang Lunyu L Mao Fei F Qian Hui H Xu Wenrong W

International journal of oncology 20170823 4

Cancer-associated mesenchymal stem cells (MSCs) are critically involved in tumor development and progression. However, the mechanisms of action for MSCs in cancer remain largely unknown. Herein, we reported that the expression of Yes-associated protein 1 (YAP) was higher in gastric cancer derived mesenchymal stem cells (GC‑MSCs) than that in bone marrow derived MSCs (BM‑MSCs). YAP knockdown not only inhibited the growth, migration and invasion, and stemness of GC‑MSCs, but also suppressed their ...[more]

PMID: 28848999

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Project description:BackgroundBone 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.MethodsGC-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.ResultsGC-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.ConclusionTumor-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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YAP signaling in gastric cancer-derived mesenchymal stem cells is critical for its promoting role in cancer progression.

Publications

YAP signaling in gastric cancer-derived mesenchymal stem cells is critical for its promoting role in cancer progression.

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