Primary tumor regulates the pulmonary microenvironment in melanoma carcinoma model and facilitates lung metastasis.
OBJECTIVE
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.
Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, 324 Jingwuweiqi Road, Jinan 250021, People's Republic of China.
Mingyong
M
Han
Jiying
J
Xu
Yuli
Y
Bi
Man
M
Jiang
Xiaoya
X
Xu
Qi
Q
Liu
Jihui
J
Jia
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D015850:Interleukin-6 / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000098:blood supply / Q000517:prevention & control* / Q000556:secondary*; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008546:Melanoma, Experimental / Q000097:blood / Q000150:complications / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000209:etiology; D011720:Pyrazoles / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000097:blood / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D059016:Tumor Microenvironment / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D014408:Biomarkers, Tumor; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D015850:Interleukin-6; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016173:Macrophage Colony-Stimulating Factor; D000068579:Celecoxib