| BACKGROUNDAccording to Cancer statistics,2012, there are790740new cases of American women tumor in2012, breast cancer has the highest proportion, accounting for29%, and has275370death cases. Breast cancer is the second leading cause of female cancer deaths, accounting for14%. In the United States, the American national cancer institute estimates that women in their lives has12%probability of breast cancer. In urban areas of our country, the total incidence rate of women with breast cancer is49-".17/10million, arranged first in the new cases of female cancer, accounting for19.62%of all new cancer cases. In rural areas of our country, the total incidence rate of breast cancer in women is16.16/10million, arranged the fifth in the new cases of female cancer, accounting for8.42%of all new cancer cases.In recent years,25%-50%of patients eventually developed into fatal metastasis after initial diagnosis and resection of the primary tumor in decades despite surgery and drug treatment has been developed. The survival and effective treatment of patients are still limited by metastasis of breast cancer.Cancer metastasis is the major cause of death in cancer patients. Metastasis is the most significant biological characteristic of malignancies,and also lead most clinical treatment failure and cause death of most cancer patients. Metastatic cascade is multi-step and involves many factors.It is influenced not only by the intrinsic properties of cancer cells, but also the microenvironment aroud. In recent years, it is increasingly recognized that inflammatory microenvironment play a major role in the process of the development of breast cancer as the malignancy development mechanism is deepening.The relationship between the inflammation and tumor metastasis become a focus for researchers.In this study, experimental animal models of inflammation and breast cancer metastasis were built to investigate the role of inflammation during breast cancer metastsis.METHODSBALB/c female mice were randomly divided into6groups:PBS group, LPS group, LT group, PT group, Cele group.LPS group, LT group, Cele group(n=10). Each group were given different treatment:①PBS group:intraperitoneal injection of PBS solution;②LPS Group:given intraperitoneal injection of LPS solution;③PT group:given PBS solution+tail vein injection of4T1cells;④LT Group:given the LPS solution+tail vein injection of4T1cells;⑤Cele group:given the LPS solution+tail vein injection of4T1cells+celecoxib by gavage. PBS、PT group mice were given the intraperitoneal injection of PBS,0.1ml (5mg/kg), for3consecutive days; LPS、LT and Cele group mice were given intraperitoneal injection of LPS,0.1ml (5mg/kg) for three days. On the fourth day, the PBS and LPS group mice were executed. Blood samples were collected by intraorbital bleeding eye, VEGF MCSF, IL-6, TNF-a levels of the plasma were measured according to the standardized protocol of ELISA kits.Collect lung tissue and the blood vessels of the lungs were compared by lung tissue pathological manifestations and immunofluorescence CD31staining. LT、PT and Cele group were injected with0.1ml4T1breast cancer cells in the cell concentration of1×x106/ml by caudal vein on the fifth day. PT、LT group mice eat free but Cele mice were given celecoxib0.5mg/Kg/d by gavage. After14days all the mice were sacrificed, and the visual observation and pathological manifestations of lung tissue were observed to compare the number of lung metastases in the two group. SPSS16.0statistical software were used for statistical analysis, the experimental data were described by mean±SD (x±s), and two samples were compared with t test. Lung tumor metastasis rate was compared with chi-square test. RESULTS1. The detection of blood plasma cytokinesLevels of VEGF in plasma of PBS group and LPS group mice were28.6±3.2ng/ml,139.1±5.7ng/ml; Levels of MCSF in plasma of PBS group and LPS group mice were5.7±1.5ng/ml,18.6±2.3ng/ml; Levels of IL-6in plasma of PBS group and LPS group mice were12.2±1.4ng/ml,15.6±2.5ng/ml; Levels of TNF-a in plasma of PBS group and LPS group mice were4.5±1.8ng/ml,50.9±4.6ng/ml.2. Inflammatory cell infiltration in lung tissueIt was observed the lung in the LPS mice were dark red with lobe edema and hyperemia; the lung in HE dyeing microscope:the alveolar wall discontinuity, intramural capillary dilatation and congestion and the alveolar space visible with a large number of red blood cells, inflammatory cells infiltration. It was observed the lung in the PBS mice were normal in size、pink; the lung in HE staining microscope: compact structure of the lungs, the alveolar wall continuous structured alveolar tissue fluid3. Vascular proliferation and changes in lung tissueRed blood vessel density of CD31antibody-labeled in the LPS group were significantly increased and the vessels were distorted.The structures were cavernous、 original and the vascular plexus was showed disorder、twisted and with internal mutually traffic.4. The effect of lung inflammation on breast cancer lung metastasisLung tissue pathology of LT and PT group showed:Of macroscopic observation, in LT group80%(8/10) tumor nodules were visible on the surface of lung tissue in mice, in PT group10%(1/10) tumor nodules were visible on the surface; HE staining: in LT group part of the alveolar wall structure were in damage, with discontinuous structure, a fibrous tissue hyperplasia, the wall of capillary dilatation and congestion, a large number of red blood cells and inflammatory cells in alveolar, airway mucosal with the large number of inflammatory cell infiltration,80%(8/10) had visible tumor tissue, within rich blood vessels, congestion, bigger tumor cells than normal cells, and a large deeply stained core, significantly increased cell number, polarity disappeared. Integrity of the alveolar wall structure in PT group was good, occasional local discontinuities, fewer inflammatory cells,20%(2/10) of mouse lungs visible tumor angiogenesis within the organization is not obvious, no significant vascular congestion.5. Effects of anti-inflammation treatment on pulmonary metastasis of breast cancerPathology performance of lung tissue in the Cele group:no tumor nodules in the surface of the lungs of mice; HE staining:the structural integrity of the alveolar walls, occasional local discontinuous, less inflammatory cells,20%(2/10) intrapulmonary tumor tissue were visible. Red blood vessel density of CD31antibody labeled was significantly smaller than the LPS group. The vessel structures were clear and regular and there was no expansion of the vascular plexus.CONCLUSION1. LPS promote the expression of cytokines and the infiltration of inflammatory cells in the tissue.2. The inflammatory environment induced by LPS may promote tumor metastasis of breast cancer and anti-inflammatory treatment can inhibit tumor metastasis of breast cancer. |
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