The ubiquitin-CXCR4 axis plays an important role in acute lung infection-enhanced lung tumor metastasis.
The ubiquitin-CXCR4 axis plays an important role in acute lung infection-enhanced lung tumor metastasis.
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DOI：
10.1158/1078-0432.ccr-13-0011
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发表时间：
2013-09-01
期刊：
影响因子：
--
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Yan L;Cai Q;Xu Y
Our goals are to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms. We combined bacteria- and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms were invested in ex vivo, in vitro, and in vivo studies. Both bacteria- and LPS-induced acute lung injury/inflammation significantly enhanced lung metastasis of four tail vein-injected mouse tumor cell lines. Bacteria also enhanced lung metastasis when 4T1 cells orthotopically injected. The broncheoalveolar lavage fluid (BALF) from LPS- or bacteria- injected mice stimulated migration of tumor cells. In vivo tracking of metastatic RM-9 cells showed that bacterial injection enhanced early dissemination of tumor cells to the lung. The majority of the BALF migratory activity could be blocked by AMD3100, a CXCR4 inhibitor. All tested cell lines expressed CXCR4. The levels of extracellular ubiquitin (Ub), but not SDF-1, in BALF were significantly increased by LPS. Ub was able to induce AMD3100-sensitive migration of tumor cells. Finally, the anti-bacterial amoxicillin and AMD3100 blocked the enhancement effect of bacterial infection on tumor metastasis. Acute lung infection dramatically increased cancer cell homing to the lung and lung metastasis. This may be due to an alteration of the lung microenvironment and preparation of a favorable metastatic “niche”. This effect was seen in multiple cancer types and thus may have broad applications for cancer patients in prevention and/or treatment of metastasis.
