Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, 324 Jingwuweiqi Road, Jinan 250021, People's Republic of China.
J Cancer Res Clin Oncol. 2013 Jan;139(1):57-65. doi: 10.1007/s00432-012-1299-7. Epub 2012 Aug 19.
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.
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.
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.
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.
肺是黑色素瘤转移的常见部位，而原发性黑色素瘤在肿瘤细胞到达之前如何影响肺部的机制尚不清楚。本研究旨在探讨原发性黑色素瘤在转移前阶段对肺部微环境的反应。
将黑色素瘤细胞（B16）植入 Balb/c 小鼠背部，通过干湿比和 H&E 染色分析肺部炎症反应，通过骨髓移植小鼠模型分析炎症细胞与转移灶的关系，通过全肺染色进一步分析肺血管，通过小鼠细胞因子阵列评估血清中促炎细胞因子的循环水平。
在转移前阶段，远处的原发性黑色素瘤会在肺部引起明显的炎症反应，炎症细胞在肿瘤细胞到达之前定植在转移前部位，而炎症细胞簇的部位是肿瘤转移部位。VEGF、M-CSF 和 TNF-α 可能是导致 B16 荷瘤小鼠转移增加的潜在因素。塞来昔布治疗对炎症反应有影响，并降低了癌症转移。
在转移前阶段，黑色素瘤会引起肺部炎症反应，改变肺部环境，从而促进肺部转移。因此，抑制肺部炎症可能为预防转移提供潜在的靶点。
