| Abstract |
Although lung cancer is a common disease, its diagnosis remains poor.
While the incidence of lung cancer has decreased in western countries,
lung cancer rates are predicted to increase generally in Asia. Studies
investigating the mutation patterns of Asian cases compared with Caucasian
types, lack adequate resources. Especially, lung cancer cell lines that
are acquired from pleural effusion exudates are rare in cell line models.
Pleural effusions in patients with NSCLC show progressive status and
malignant features. In our study, 28 lung cancer cell lines derived from
pleural effusions were newly established and their cellular and molecular
characteristics were analyzed. Representative mutations in BRAF, EGFR,
ERBB2, FGFR4, KRAS and TP53 as well as fusions such as ALK, CD74 and RET
genes were detected and validated. Based on mutation profiles, drug
sensitivities to gefitinib, erlotinib and crizotinib were measured. Cell
lines that carry target mutations to each drug are generally sensitive.
Cell lines originating from pleural effusions are relatively more
resistant than cell lines derived from tissues that harbor similar
mutation. Analysis of mutational pattern and drug sensitivity of these
cell lines can facilitate database construction for case study. Expression
levels of specific oncoproteins such as ERK, ERBB2, c-MET and PTEN were
detected in our cell lines. EMT markers such as EpCAM, E-cadherin,
N-cadherin and Vimentin were also detected. These 28 well characterized lung
cancer cell lines originating from malignant pleural effusions support
studies associated with sensitivity to anti-cancer drugs and
representative mutations in lung cancers. the few experimental results and
small patient numbers still limit our knowledge of the acquired resistance
to crizotinib. To meet this need, we established crizotinib-resistant
sublines. Their parental cell lines were derived from a pleural effusion
exudate which was thought to be more aggressive and resistant to anti-
cancer drugs.
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