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.
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.
Authors: Purevdorj B Olkhanud; Dolgor Baatar; Monica Bodogai; Fran Hakim; Ronald Gress; Robin L Anderson; Jie Deng; Mai Xu; Susanne Briest; Arya Biragyn Journal: Cancer Res Date: 2009-06-30 Impact factor: 12.701
Authors: Sachie Hiratsuka; Shom Goel; Walid S Kamoun; Yoshiro Maru; Dai Fukumura; Dan G Duda; Rakesh K Jain Journal: Proc Natl Acad Sci U S A Date: 2011-02-14 Impact factor: 11.205
Authors: Rose Du; Kan V Lu; Claudia Petritsch; Patty Liu; Ruth Ganss; Emmanuelle Passegué; Hanqiu Song; Scott Vandenberg; Randall S Johnson; Zena Werb; Gabriele Bergers Journal: Cancer Cell Date: 2008-03 Impact factor: 31.743
Authors: Rosandra N Kaplan; Rebecca D Riba; Stergios Zacharoulis; Anna H Bramley; Loïc Vincent; Carla Costa; Daniel D MacDonald; David K Jin; Koji Shido; Scott A Kerns; Zhenping Zhu; Daniel Hicklin; Yan Wu; Jeffrey L Port; Nasser Altorki; Elisa R Port; Davide Ruggero; Sergey V Shmelkov; Kristian K Jensen; Shahin Rafii; David Lyden Journal: Nature Date: 2005-12-08 Impact factor: 49.962