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Primary tumor regulates the pulmonary microenvironment in melanoma carcinoma model and facilitates lung metastasis

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Abstract

Purpose

Lung is a common site for the occurrence of melanoma metastasis, the mechanism by which primary melanoma affects the lungs before tumor cells arrival is poorly understood. The aim of this study was to explore lung microenvironment response to primary melanoma in the premetastatic phase.

Methods

Melanoma cells (B16) were implanted into the Balb/c mice back, pulmonary inflammation response was analyzed by wet/dry ratios and H&E staining, the relationship between inflammation cells and metastatic foci was analyzed by bone marrow transplant mouse model, pulmonary vasculature was further analyzed by whole mount staining, and the circulating levels of proinflammatory cytokines in sera were evaluated by mouse cytokine array.

Results

In the premetastatic stage, significant inflammation response in lungs was induced by a distant primary melanoma, inflammation cells colonize in premetastatic sites before tumor cells arrived, and the sites of inflammation cells clusters are tumor metastasis sites. VEGF, M-CSF and TNF-α may be the underlying factors responsible for the increased metastasis in the B16-bearing mice. Treatment with celecoxib had effects on inflammation response and reduced cancer metastasis.

Conclusions

In the premetastatic phase, the melanoma induces pulmonary inflammation response, changes the lung environment and then facilitates lung metastasis. Thus, inhibition of lung inflammation may provide potential targets for the prevention of metastasis.

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Acknowledgments

This work was supported by General programs of Natural Science Foundation of Shandong Province (No. BS2009SW050) and Key Development Program for Basic Research of Shandong Province (2007GG20002007).

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, 324 Jingwuweiqi Road, Jinan, 250021, People’s Republic of China

    Mingyong Han, Jiying Xu, Yuli Bi, Man Jiang, Xiaoya Xu & Qi Liu

  2. Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, People’s Republic of China

    Jihui Jia

Authors
  1. Mingyong Han
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  2. Jiying Xu
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  3. Yuli Bi
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  4. Man Jiang
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  5. Xiaoya Xu
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  6. Qi Liu
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  7. Jihui Jia
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Correspondence to Qi Liu or Jihui Jia.

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Han, M., Xu, J., Bi, Y. et al. Primary tumor regulates the pulmonary microenvironment in melanoma carcinoma model and facilitates lung metastasis. J Cancer Res Clin Oncol 139, 57–65 (2013). https://doi.org/10.1007/s00432-012-1299-7

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  • DOI: https://doi.org/10.1007/s00432-012-1299-7

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