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Tumor Biology

, Volume 35, Issue 5, pp 4285–4293 | Cite as

The mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa shift peritoneal milky spot macrophages towards an M1 phenotype to dampen peritoneal dissemination

  • Zhi-Feng Miao
  • Ting-Ting Zhao
  • Feng Miao
  • Zhen-Ning Wang
  • Ying-Ying Xu
  • Xiao-Yun Mao
  • Jian Gao
  • Jian-Hua Wu
  • Xing-Yu Liu
  • Yi You
  • Hao Xu
  • Hui-Mian Xu
Research Article
  • 230 Downloads

Abstract

Peritoneal dissemination (PD) of tumor cells is the most frequent pattern of gastric cancer recurrence and the leading cause of death. Peritoneal milky spots are deemed as the site of origin of gastric cancer PD wherein the main cellular components are macrophages. A vaccine derived from the mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa (PA-MSHA) has exhibit strong immune modulatory properties. In the present study, we tested the hypothesis whether the PA-MSHA vaccine activated peritoneal milky spot macrophages (PMSM) in a manner that would attenuate PD. It was observed that PA-MSHA activated PMSM towards a classical activation phenotype via a toll-like receptor4/9-dependent mechanism, which increased interleukin-12 levels and promoted the expression of co-stimulatory and antigen-presenting molecules like CD80, CD86, and MHC-II (P < 0.05). In addition, PA-MSHA-treated PMSM exhibited strong nonspecific antitumor effects in both contact-dependent and contact-independent modes of action (P < 0.05). In mice treated with PA-MSHA before inoculating gastric cancer cells, we noted alleviated PD toward the untreated mice. In conclusion, our findings demonstrated that PA-MSHA can stimulate PMSM towards an M1 phenotype and that activated PMSM inhibit gastric cancer growth and PD both in vitro and in vivo. The results of the current study provide a mechanistic insight that is relevant to the potential application of PA-MSHA in the treatment of gastric cancer-mediated PD.

Keywords

Peritoneal carcinomatosis Stomach cancer Peritoneal macrophage Immunotherapy PA-MSHA Inflammatory cytokines 

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Zhi-Feng Miao
    • 1
  • Ting-Ting Zhao
    • 2
  • Feng Miao
    • 3
  • Zhen-Ning Wang
    • 1
  • Ying-Ying Xu
    • 2
  • Xiao-Yun Mao
    • 2
  • Jian Gao
    • 4
  • Jian-Hua Wu
    • 1
  • Xing-Yu Liu
    • 1
  • Yi You
    • 1
  • Hao Xu
    • 1
  • Hui-Mian Xu
    • 1
  1. 1.Department of Surgical OncologyThe First Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Breast SurgeryThe First Affiliated Hospital of China Medical UniversityShenyangChina
  3. 3.Department of DigestionThe Fourth Affiliated Hospital of China Medical UniversityShenyangChina
  4. 4.Center of Laboratory Technology and Experimental MedicineChina Medical UniversityShenyangChina

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