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

Li W, Zhou Y, Yang J, Zhang X, Zhang H, Zhang T, Zhao S, Zheng P, Huo J, Wu H - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: Bone marrow mesenchymal stem cells (BM-MSCs) have been identified to be closely associated with tumor growth and progression.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.

View Article: PubMed Central - PubMed

Affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. medical112@126.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Tumor-promoting effect of GC-MSCs on BGC-823 cells is attenuated by the application of anti-IL-8 antibody. (A) Cytokine profile analysis of GC-MSCs, GCN-MSCs, or BM-MSCs by Luminex immunoassay. (B) Viability of BGC-823 cells cultured in 10 % GC-MSC-CM treated with or without anti-IL-8 antibody by MTT assay. (C) Transwell migration assay of BGC-823 cells exposed to 10 % GC-MSC-CM with or without anti-IL-8 antibody treatment (×200). (D) Expression of VEGF, MIP-1, IL-6, and IL-8 in BGC-823 cells exposed to 10 % GC-MSC-CM with or without IL-8 blockade. (E) Western blot for protein levels of Akt, p-Akt, p44/42 MAPK (Erk1/2), and p-p44/42 MAPK (Erk1/2) in BGC-823 cells stimulated by 10 % GC-MSC-CM with or without IL-8 blockade. (F) Representative photographs of capillary tube formation by HUVECs exposed to 10 % GC-MSC-CM with or without IL-8 blockade. (×100). *P < 0.05, **P < 0.01: compared with the control group; #P < 0.05, ##P < 0.01: compared with the GC-MSC-CM treated group
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4443537&req=5

Fig7: Tumor-promoting effect of GC-MSCs on BGC-823 cells is attenuated by the application of anti-IL-8 antibody. (A) Cytokine profile analysis of GC-MSCs, GCN-MSCs, or BM-MSCs by Luminex immunoassay. (B) Viability of BGC-823 cells cultured in 10 % GC-MSC-CM treated with or without anti-IL-8 antibody by MTT assay. (C) Transwell migration assay of BGC-823 cells exposed to 10 % GC-MSC-CM with or without anti-IL-8 antibody treatment (×200). (D) Expression of VEGF, MIP-1, IL-6, and IL-8 in BGC-823 cells exposed to 10 % GC-MSC-CM with or without IL-8 blockade. (E) Western blot for protein levels of Akt, p-Akt, p44/42 MAPK (Erk1/2), and p-p44/42 MAPK (Erk1/2) in BGC-823 cells stimulated by 10 % GC-MSC-CM with or without IL-8 blockade. (F) Representative photographs of capillary tube formation by HUVECs exposed to 10 % GC-MSC-CM with or without IL-8 blockade. (×100). *P < 0.05, **P < 0.01: compared with the control group; #P < 0.05, ##P < 0.01: compared with the GC-MSC-CM treated group

Mentions: Since GC-MSCs were demonstrated to affect proliferation, migration, and angiogenesis of gastric cancer in a paracrine manner, the key factors contributing to the tumor-promoting role of GC-MSCs were further analyzed in this study. Cytokines/chemokines including VEGF, MCP-1, IL-6, and IL-8 were detectable in the supernatant of GC-MSCs, GCN-MSCs, or BM-MSCs, whereas GC-MSCs elaborated a strikingly higher level of IL-8 secretion with significant difference from GCN-MSC-CM or BM-MSC-CM (P < 0.01) (Fig. 7A). Along these lines, we postulate that the tumor-promoting effect of GC-MSCs may be partly mediated by IL-8 secretion.Fig. 7


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

Li W, Zhou Y, Yang J, Zhang X, Zhang H, Zhang T, Zhao S, Zheng P, Huo J, Wu H - J. Exp. Clin. Cancer Res. (2015)

Tumor-promoting effect of GC-MSCs on BGC-823 cells is attenuated by the application of anti-IL-8 antibody. (A) Cytokine profile analysis of GC-MSCs, GCN-MSCs, or BM-MSCs by Luminex immunoassay. (B) Viability of BGC-823 cells cultured in 10 % GC-MSC-CM treated with or without anti-IL-8 antibody by MTT assay. (C) Transwell migration assay of BGC-823 cells exposed to 10 % GC-MSC-CM with or without anti-IL-8 antibody treatment (×200). (D) Expression of VEGF, MIP-1, IL-6, and IL-8 in BGC-823 cells exposed to 10 % GC-MSC-CM with or without IL-8 blockade. (E) Western blot for protein levels of Akt, p-Akt, p44/42 MAPK (Erk1/2), and p-p44/42 MAPK (Erk1/2) in BGC-823 cells stimulated by 10 % GC-MSC-CM with or without IL-8 blockade. (F) Representative photographs of capillary tube formation by HUVECs exposed to 10 % GC-MSC-CM with or without IL-8 blockade. (×100). *P < 0.05, **P < 0.01: compared with the control group; #P < 0.05, ##P < 0.01: compared with the GC-MSC-CM treated group
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4443537&req=5

Fig7: Tumor-promoting effect of GC-MSCs on BGC-823 cells is attenuated by the application of anti-IL-8 antibody. (A) Cytokine profile analysis of GC-MSCs, GCN-MSCs, or BM-MSCs by Luminex immunoassay. (B) Viability of BGC-823 cells cultured in 10 % GC-MSC-CM treated with or without anti-IL-8 antibody by MTT assay. (C) Transwell migration assay of BGC-823 cells exposed to 10 % GC-MSC-CM with or without anti-IL-8 antibody treatment (×200). (D) Expression of VEGF, MIP-1, IL-6, and IL-8 in BGC-823 cells exposed to 10 % GC-MSC-CM with or without IL-8 blockade. (E) Western blot for protein levels of Akt, p-Akt, p44/42 MAPK (Erk1/2), and p-p44/42 MAPK (Erk1/2) in BGC-823 cells stimulated by 10 % GC-MSC-CM with or without IL-8 blockade. (F) Representative photographs of capillary tube formation by HUVECs exposed to 10 % GC-MSC-CM with or without IL-8 blockade. (×100). *P < 0.05, **P < 0.01: compared with the control group; #P < 0.05, ##P < 0.01: compared with the GC-MSC-CM treated group
Mentions: Since GC-MSCs were demonstrated to affect proliferation, migration, and angiogenesis of gastric cancer in a paracrine manner, the key factors contributing to the tumor-promoting role of GC-MSCs were further analyzed in this study. Cytokines/chemokines including VEGF, MCP-1, IL-6, and IL-8 were detectable in the supernatant of GC-MSCs, GCN-MSCs, or BM-MSCs, whereas GC-MSCs elaborated a strikingly higher level of IL-8 secretion with significant difference from GCN-MSC-CM or BM-MSC-CM (P < 0.01) (Fig. 7A). Along these lines, we postulate that the tumor-promoting effect of GC-MSCs may be partly mediated by IL-8 secretion.Fig. 7

Bottom Line: Bone marrow mesenchymal stem cells (BM-MSCs) have been identified to be closely associated with tumor growth and progression.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.

View Article: PubMed Central - PubMed

Affiliation: Center of Research Laboratory, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang, 222001, China. medical112@126.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus