Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapy. In present study, we identified a subpopulation of cells isolated from the A549 cell line with marker CD133. In vivo results showed that A549 CD133 + cells displayed high liver metastatic potential. Severe liver cell damage with tumor cell invasion revealed by pathological examination and these changes were consistent with the results of serological tests where the plasma GPT and GOT level are significantly higher than that of the control group. Compared with A549 cells, A549 CD133 + cells expressed high levels of VEGF and exhibited high migration and invasion capability. In conclusion, we first reported that A549 CD133 + cells exhibited characteristic of high liver metastatic potential which makes it be a suitable model for further study of liver metastasis of lung adenocarcinoma and provide a potential platform for antimetastatic drug discovery or evaluation.
Key words: human lung adenocarcinoma, liver metastasis, migration, invasion, CD133Lung cancer is one of the most aggressive neoplasms in the world [1]. Despite management and treatment of lung cancer has been improved these years, but the prognosis remains poor, the 5-year survival rate of non-small cell lung cancer (NSCLC) is no more than 15 % [2]. Approximately 50 % of NSCLC patients with stage I and II will die from recurrent disease despite conventional therapy, and nearly 70% of lung cancer patients will die from metastatic disease, even after surgical resection of the primary tumor, radiation therapy, and chemotherapy [3]. Thus, it is important to find novel effective therapies to inhibit lung cancer metastasis.The most common four metastatic sites of patients with solitary metastatic NSCLC were: bone, liver, kidney and spleen [3]. Nevertheless, the mechanism of which lung adenocarcinoma selectively disseminated to certain organs remains unknown. However, experimental reproducible animal models facilitate to understand the process of metastasis and can provide suitable models for basic or preclinical studies.Different kinds of cancer metastasis model have been published yet. Early in 1996, Iguchi H et al [4] have established lung cancer metastasis model with human lung squamous cell carcinoma-derived cells (HARA). In 1959, Leduc [5] was the first to describe liver metastasis in mice after injection of hepatoma carcinoma cells in the spleen. Moreover, the liver metastasis models in nude mice of colon carcinoma have been successfully established [6,7]. Early studies in immunodeficient mice illustrated that subcutaneous injection of tumor cells seldom give rise to liver metastases [8].However, no lung adenocarcinoma liver metastasis model has been published so far. CD133 as a marker of cancer stem cells (CSCs) has been demonstrated in many cancers including lung cancer [9][10][11][12][13]. The CSCs theory indicated that subpopulation of tumor cells with stem or progenitor cell characteristics c...