Establishment of a highly metastatic model with a newly isolated lung adenocarcinoma cell line

Abstract

Abstract. Lung cancer is the leading cause of malignancyrelated death worldwide, and metastasis always results in a poor prognosis. However, therapeutic progress is hampered by a deficiency of appropriate pre-clinical metastatic models. To bridge this experimental gap, we developed an in vivo metastatic model via subcutaneous (s.c.) injection. The original cell line (XL-2) adopted in this model was newly isolated from the ascites of a patient with extensive metastases of lung adenocarcinoma, thereby avoiding any alteration of its initial molecular biology features from artificial serial cultivation. After comprehensive phenotypical and histological analysis, it was identified as a lung adenocarcinoma cell line. Additionally, the drug test showed that XL-2 cell line was sensitive to docetaxel, and resistant to doxorubicin, indicating it might serve as a cell line model of drug resistance for identifying mechanisms of tumors resistant to doxorubicin. Through this s.c. model, we further obtained a highly metastatic cell line (designated XL-2sci). The metastatic rate of mice in XL-2 group was 3/10, in contrast to the rate of 9/10 in XL-2sci group. Optical imaging, micro-computed tomography (micro-CT) scanning and Transwell assays were further applied to identify the enhanced metastatic capacity of Xl-2sci cells both in vivo and in vitro. Compared with XL-2 cells, ITRAQ labeled proteomics profiling study showed that some tumor metastasisassociated proteins were upregulated in XL-2sci cells, which also indicated the reliability of our model. Proliferation ability of XL-2 and XL-2sci were also evaluated. Results showed that highly metastatic XL-2sci possessed a decreased proliferation capacity versus XL-2, which demonstrated that its increased metastatic activity was not facilitated by a faster growth rate.In conclusion, we successfully developed an in vivo metastatic model using a newly established lung adenocarcinoma cell line, which will be beneficial to further investigations of lung cancer metastasis and to the development of anti-metastasis drugs.

OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer

“…All cell lines were cultured according to ATCC protocols and supplemented with 10% fetal bovine serum (FBS) (Biowest, South America Origin, Nuaille, France), 100 U/mL penicillin sodium, and 100 µg/mL streptomycin sulfate at 37 °C in a humidified incubator under 5% carbon dioxide. XL-2 and LC-21 cells were established by our laboratory 25, 26. Cells were used when they were in the logarithmic growth phase.…”

Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma

“…However, exposure of highly metastatic melanoma cells to hypoxia led to a significant downregulation of Tip110 together with TP53 in both in vitro and in a melanoma cancer bone metastasis mouse model [ 3 ]. Also, Tip110 expression was found to be dysregulated and correlated with a metastatic phenotype in melanoma and lung adenocarcinoma [ 4 , 5 ]. Therefore, it is plausible that differential expression of Tip110 could be an indicator for melanoma tumorigenesis.…”

Overcoming the leptomeningeal seeding of medulloblastoma by targeting HSP70

“…For the enhanced LMS mouse model, the mice were sacri ced when spinal LMS was observed in bioluminescence imaging (BLI), and then the brain and spine were separately harvested. The tumor cells were extracted from the brain and spine tissues of the mouse and cultured as described previously [20][21][22][23][24]. When the number of cells reached 1 × 10 7 cells, magnetic-activated cell sorting (MACS, Miltenyi Biotech Ltd., Bergisch Gladbach, Germany) was performed using a monoclonal anti-CD90.1 conjugated to magnetic microbeads as described previously [10].…”