Establishment and Characterization of a Pair of Patient-derived Human Non-small Cell Lung Cancer Cell Lines from a Primary Tumor and Corresponding Lymph Node Metastasis

建立并鉴定一对源自原发性肿瘤和相应淋巴结转移的患者来源的人类非小细胞肺癌细胞系

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作者:Florian Gebauer, Daniel Wicklein, Michael Tachezy, Tobias Grob, Doris Steinemann, Georgi Manukjan, Gudrun Göhring, Brigitte Schlegelberger, Hanna Maar, Jakob R Izbicki, Maximilian Bockhorn, Udo Schumacher

Background

Non-small lung cancer is the leading cause of cancer-related mortality worldwide. For a deeper understanding of tumor biology, we established a pair of cell lines derived from a primary tumor and a corresponding lymph node metastasis. Material and

Conclusion

We provide detailed analysis of a cell line derived from a primary tumor and a corresponding LN metastasis. This unique feature allows further investigative analysis of the differences and regulatory processes underlying the metastatic process during tumor progression in non-small cell lung cancer.

Material and methods

The cell line BC4323 from the primary tumor (PT) and a mediastinal lymph node metastasis (LN) were derived from an adenocarcinoma (pT2, pN2, G3, UICC stage IIIa) in a 47-year-old female patient. Comparative characterization was performed by in vitro analysis. A murine xenograft was established for analysis of in vivo behavior.

Methods

The cell line BC4323 from the primary tumor (PT) and a mediastinal lymph node metastasis (LN) were derived from an adenocarcinoma (pT2, pN2, G3, UICC stage IIIa) in a 47-year-old female patient. Comparative characterization was performed by in vitro analysis. A murine xenograft was established for analysis of in vivo behavior.

Results

Chromosomal aberrations were detected in multiple chromosomal sections throughout the entire genome, with only a few differences between PT and LN cells. High-level Kirsten ras oncogene homolog (KRAS) mutation and amplification were seen based on a chromosomal translocation and novel assembled chromosome. In contrast to the genomic level, at the mRNA and protein levels, multiple differences were detectable, in particular in markers for cell adhesion [e.g. epithelial cell adhesion molecule (EpCAM), CD44, P-selectin binding, epidermal growth factor receptor (EGFR) and integrin alphaV] and the epithelial-mesenchymal transition. Due to accelerated tumor growth in vivo by the PT cells, a shortened overall survival was seen (60 vs. 101 days, p=0.005).

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