Inflammation is a potent promoter of tumor metastasis. The aim of the present study was to explore the function of systemic inflammation in the formation of lung metastasis of breast cancer cells in a mouse model. BALB/c mice were injected intraperitoneally with lipopolysaccharide (LPS) in order to establish an inflammatory animal model and 4T1 murine breast cancer cells were injected through the tail vein to induce lung metastasis. The levels of proinflammatory cytokines were evaluated by ELISA. Metastases on the surface of the lungs were counted and histologically analyzed by hematoxylin and eosin staining. Angiogenesis in the lungs was examined by CD31 immunofluorescence. Mouse pulmonary endothelial cells (MPVECs) were isolated and used to assay endothelial tube formation and determine the protein expression levels of vascular endothelial growth factor (VEGF) in vitro. Serum levels of VEGF and prostaglandin E2 (PGE2), the number and size of metastatic lesions, and the expression levels of cyclooxygenase‑2 were significantly greater in the lungs of LPS‑treated mice, as compared with those in control mice threated with phosphate‑buffered saline. Blood vessel density was also markedly increased in the LPS‑treated mice. These increases were reversed by treatment with celecoxib. In vitro, the protein expression levels of VEGF produced by the PGE2‑treated cells were significantly increased in a concentration‑dependent manner. In addition, the production of VEGF was increased in response to treatment with the PGE2 receptor (EP2) agonist ONO‑AE1‑259‑01; however, this increase was abrogated by treatment with AH6809, an EP2 receptor antagonist. Treatment with PGE2 or VEGF alone promoted the tube formation of MPVECs and this effect was reversed by treatment with celecoxib. These results demonstrated that PGE2 may regulate the release of VEGF by MPVECs through the EP2 receptor pathway and thereby promoted pulmonary angiogenesis and breast cancer metastasis in a mouse model.

PurposeThe prognosis of lung cancer with brain metastasis is poor. The purpose of this study was to investigate the distribution of brain metastasis and explore its relationship with pathology and genetic mutations.Patients and methodsBetween June 2015 and July 2018, 335 patients from Shandong Provincial Hospital affiliated to Shandong University who had been firstly diagnosed with brain metastasis from lung cancer were retrospectively reviewed. All metastatic lesions were detected in the corresponding area using magnetic resonance imaging (MRI).ResultsA total of 2046 metastatic lesions were found. Of the 335 patients, 21.2% (71/335) had a single brain metastasis and 78.8% (264/335) had multiple lesions. The cerebellum (56%; 189/335), right parietal lobe (54%; 182/335), right frontal lobe (47%; 157/335), and left frontal lobe (45%; 152/335) were the regions with the highest incidence of brain metastasis. The different pathological types of lung cancer showed different distribution of brain metastasis. In lung adenocarcinoma, the left frontal lobe (53%; 111/208), right frontal lobe (48%; 100/208) and cerebellum (56%; 116/208) exhibited higher brain metastases, while the cerebellum (61%; 45/74) and the right frontal lobe (46%; 34/74) had the highest incidence of brain metastasis from small-cell carcinoma. For lung squamous cell carcinoma, the cerebellum (70%; 14/20) was the most common site for metastasis. Adenocarcinoma was the most common pathological type in patients regardless of the number of lesions (ie, single or multiple brain metastases). Comparison of 37 cases with epidermal growth factor receptor (EGFR) gene mutation versus 26 cases without mutations showed that there was no correlation between the distribution of brain metastasis and gene mutation.ConclusionThe different pathological types of lung cancer demonstrate different distribution of brain metastasis. These findings may have significant implications in the diagnosis and treatment of brain metastasis from lung cancer.

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