YZ and JY collected bone marrow and tumor tissues, and carried out the MSCs isolations. 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 LY450108 or BM-MSCs. Blockade of IL-8 by neutralizing LY450108 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. test using SPSS 16.0 statistical software, and (Fig.?1A). After plated into LY450108 flasks, the cells exhibited spindle-shaped morphology, which were similar to GCN-MSCs or BM-MSCs (Fig.?(Fig.1A).1A). Moreover, the pluripotent differentiation potential of GC-MSCs was evaluated and compared it with non-malignant tissue-derived GCN-MSCs and BM-MSCs. In addition, we further investigated the underlying mechanism involved in the tumor-promoting effect of GC-MSCs. Firstly, we observed the influence of GC-MSCs in gastric cancer cell proliferation. The results showed that BGC-823 and MKN-28 cells were both stimulated to grow faster when incubated with 10?% GC-MSC-CM, which displayed a more potent tumor-promoting ability than GCN-MSC-CM or BM-MSC-CM. This suggests a pivotal role of gastric cancer-resident MSCs in tumor cell proliferation. In keeping with GluN2A our results, Guangwen, and colleagues reported that mouse lymphoma-derived MSCs present a more potently effect of tumor growth-promotion than BM-MSCs or MSCs from other normal tissues such as skin [16]. Another study also conveyed that MSCs from human breast cancer tissues have certain increased effect on the growth of breast malignancy [32]. Consequently, we investigated the effect of GC-MSCs on gastric cancer cell recruitment by a transwell migration assay. A more drastic promotion was observed in the migration of gastric cancer cells with 10?% GC-MSC-CM stimulation compared with 10?% GCN-MSC-CM or BM-MSC-CM treatment, suggesting a greater potential of GC-MSCs to promote gastric cancer metastasis. Furthermore, the pro-angiogenic role of GC-MSCs has drawn much interest in the present study, which may be involved in gastric cancer growth and metastasis. Ting and colleagues found that the crosstalk between tumor cells and BM-MSCs could increase the expression of pro-angiogenic factors and thereby promote growth and angiogenesis of breast and prostate tumors [14]. Another report proposed that MSC-secreted IL-6 may enrich the pro-angiogenic factors secreted by cancer cells to increase angiogenesis and tumor growth, and targeting this conversation may lead to novel therapeutic and preventive strategies [33]. In our study, GC-MSCs expressed higher levels of VEGF, MIP-2, TGF-1, IL-6, and IL-8 than GCN-MSCs or BM-MSCs did, suggesting a more potent role of GC-MSCs in tumor angiogenesis. Consequently, we investigated the effect of gastric cancer cell-derived CM around the pro-angiogenic ability of GC-MSCs and observed an appreciable increase of VEGF both in mRNA and protein levels. Moreover, the expressions of VEGF, MIP-2, TGF-1, IL-6, and IL-8 were all up-regulated in GCN-MSCs and BM-MSCs by 10?% BGC-823-CM or MKN-28-CM stimulation, suggesting a converted progression suffered by MSCs from non-malignant tissues by tumor cells. On the other hand, BGC-823, or MKN-28 cells exposed to 10?% GC-MSC-CM presented appreciable increase in pro-angiogenic ability, which may be associated with the marketing promotions of growth and metastasis in gastric cancer. How did GC-MSCs stimulate the proliferation, migration, and angiogenesis of gastric cancer cells? The underlying mechanism was further investigated in our study. According to the report by Yun and colleagues, IL-8 could stimulate VEGF production in BM-MSCs in part via the PI3K/Akt and MAPK/ERK signal pathways and administration of IL-8 treated BM-MSCs increases angiogenesis after.