Tumor Biology

, Volume 37, Issue 5, pp 6913–6921 | Cite as

The MSHA strain of Pseudomonas aeruginosa (PA-MSHA) inhibits gastric carcinoma progression by inducing M1 macrophage polarization

  • Changming Wang
  • Zunqi Hu
  • Zhenxin Zhu
  • Xin Zhang
  • Ziran Wei
  • Yu Zhang
  • Dali Hu
  • Qingping Cai
Original Article


Macrophages play crucial roles in promoting tumor development and progression. In the present study, we found that the mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa (PA-MSHA) was efficient in inducing M1 macrophage polarization. PA-MSHA treatment increases expression of M1-related cytokines and promotes activation of murine peritoneal macrophages (MPM). Interestingly, PA-MSHA inhibits cell proliferation and migration and induces the apoptosis of gastric carcinoma cells. These effects of PA-MSHA on M1 polarization were associated with activation of NF-κB expression. Thus, inducing polarization of M1 by PA-MSHA may be one potential strategy for inhibiting gastric carcinoma progression in mice.


PA-MSHA Gastric carcinoma M1 polarization NF-κB 



This work was carried out with the support of “Youth start-up Foundation of Changzheng hospital (Project No. 2013CZQN10).”

Compliance with ethical standards

The animal experiment was carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals, with the approval of the Scientific Investigation Board of the Second Military Medical University (Shanghai, China).

Conflicts of interest



  1. 1.
    Zhou Z, Ji Z, Wang Y, Li J, Cao H, Zhu HH, et al. TRIM59 is up-regulated in gastric tumors, promoting ubiquitination and degradation of p53. Gastroenterology. 2014;147:1043–54.CrossRefPubMedGoogle Scholar
  2. 2.
    Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRefPubMedGoogle Scholar
  3. 3.
    Blaylock RL. Cancer microenvironment, inflammation and cancer stem cells: a hypothesis for a paradigm change and new targets in cancer control. Surg Neurol Int. 2015;6:92.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Solinas G, Germano G, Mantovani A, Allavena P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 2009;86:1065–73.CrossRefPubMedGoogle Scholar
  5. 5.
    Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010;32:593–604.CrossRefPubMedGoogle Scholar
  6. 6.
    Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141:39–51.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Biswas SK, Chittezhath M, Shalova IN, Lim JY. Macrophage polarization and plasticity in health and disease. Immunol Res. 2012;53:11–24.CrossRefPubMedGoogle Scholar
  8. 8.
    Schroeder GN, Hilbi H. Cholesterol is required to trigger caspase-1 activation and macrophage apoptosis after phagosomal escape of Shigella. Cell Microbiol. 2007;9:265–78.CrossRefPubMedGoogle Scholar
  9. 9.
    Galmbacher K, Heisig M, Hotz C, Wischhusen J, Galmiche A, Bergmann B, et al. Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression. PLoS One. 2010;5, e9572.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hou J, Liu Y, Shao Y. The MSHA strain of Pseudomonas aeruginosa activated TLR pathway and enhanced HIV-1 DNA vaccine immunoreactivity. PLoS One. 2012;7, e47724.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Li T, Dong ZR, Guo ZY, Wang CH, Zhi XT, Zhou JW, et al. Mannose-mediated inhibitory effects of PA-MSHA on invasion and metastasis of hepatocellular carcinoma via EGFR/Akt/IkappaBbeta/NF-kappaB pathway. Liver Int. 2015;35:1416–29.CrossRefPubMedGoogle Scholar
  12. 12.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25:402–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Rabender CS, Alam A, Sundaresan G, Cardnell RJ, Yakovlev VA, Mukhopadhyay ND, et al. The role of nitric oxide synthase uncoupling in tumor progression. Mol Cancer Res. 2015;13:1034–43.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Meitzler JL, Antony S, Wu Y, Juhasz A, Liu H, Jiang G, et al. NADPH oxidases: a perspective on reactive oxygen species production in tumor biology. Antioxid Redox Signal. 2014;20:2873–89.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Lee JJ, Kwon HK, Lee DS, Lee SW, Lee KK, Kim KJ, et al. Mycelial extract of Phellinus linteus induces cell death in A549 lung cancer cells and elevation of nitric oxide in raw 264.7 macrophage cells. Mycobiology. 2006;34:143–7.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Biswas SK, Lewis CE. NF-kappaB as a central regulator of macrophage function in tumors. J Leukoc Biol. 2010;88:877–84.CrossRefPubMedGoogle Scholar
  17. 17.
    Mancino A, Lawrence T. Nuclear factor-kappaB and tumor-associated macrophages. Clin Cancer Res. 2010;16:784–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Blank T, Prinz M. NF-kappaB signaling regulates myelination in the CNS. Front Mol Neurosci. 2014;7:47.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Zhang QW, Liu L, Gong CY, Shi HS, Zeng YH, Wang XZ, et al. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS One. 2012;7, e50946.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Pantano F, Berti P, Guida FM, Perrone G, Vincenzi B, Amato MM, et al. The role of macrophages polarization in predicting prognosis of radically resected gastric cancer patients. J Cell Mol Med. 2013;17:1415–21.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Mahbub S, Deburghgraeve CR, Kovacs EJ. Advanced age impairs macrophage polarization. J Interferon Cytokine Res. 2012;32:18–26.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Liu ZB, Hou YF, Zhu J, Hu DL, Jin W, Ou ZL, et al. Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner. Oncogene. 2010;29:2996–3009.CrossRefPubMedGoogle Scholar
  23. 23.
    Buttari B, Profumo E, Segoni L, D’Arcangelo D, Rossi S, Facchiano F, et al. Resveratrol counteracts inflammation in human M1 and M2 macrophages upon challenge with 7-oxo-cholesterol: potential therapeutic implications in atherosclerosis. Oxid Med Cell Longev. 2014;2014:257543.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Changming Wang
    • 1
  • Zunqi Hu
    • 1
  • Zhenxin Zhu
    • 1
  • Xin Zhang
    • 1
  • Ziran Wei
    • 1
  • Yu Zhang
    • 1
  • Dali Hu
    • 2
  • Qingping Cai
    • 1
  1. 1.Gastrointestinal Surgery Department, Shanghai Changzheng HospitalSecond Military Medical UniversityShanghaiChina
  2. 2.Research and Medical DepartmentBeijing Wanter Bio-pharmaceutical Co., LtdBeijingChina

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