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Establishment of lung cancer patient-derived xenograft models and primary cell lines for lung cancer study

Authors :
Yanan Jiang
Jimin Zhao
Yi Zhang
Ke Li
Tiepeng Li
Xinhuan Chen
Simin Zhao
Song Zhao
Kangdong Liu
Ziming Dong
Source :
Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-18 (2018)
Publication Year :
2018
Publisher :
BMC, 2018.

Abstract

Abstract Background The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patient-derived xenografts (PDX) models and primary cells are both used to screen therapeutic regimens for cancer. However, PDX models and primary cells from the same patient are difficult to establish. Their consistency to the original tumor tissue is not well studied. Methods 31 lung cancer patient tissues were procured to establish the lung cancer PDX models and primary cell lines. Tumor growth measurements, histological and immunohistochemistry analysis, Western blotting, EGFR and K-RAS mutation detection and gefitinib sensitive assay were performed to evaluate the characteristic of established PDX models. Immunofluorescence analysis, anchorage-independent cell growth, Western blotting and gefitinib sensitive assay were performed to assay the characteristic of established primary cell lines. The whole-exome sequencing was used to compare the characteristic of the patient’s tumor tissue, established PDX and primary cell line. Results Twenty-one lung cancer PDX models (67.74%, 21/31) and ten primary cell lines (32.25%, 10/31) were established from patients’ tumor tissues. The histology and pathological immunohistochemistry of PDX xenografts are consistent with the patients’ tumor samples. Various signal pathways were activated in different PDX models (n = 5) and primary cell lines (n = 2). EGFR mutation PDX model and primary cell line (LG1) were sensitive to gefitinib treatment. The expression of CK8/18, TTF1 and NapsinA in LG1 and LG50 primary cells were also positive. And the activated signal pathways were activated in LG1 and LG50 primary cell lines. Furthermore, the gene mutation in PDX tumor tissues and primary cell line (LG50) was consistent with the mutation in LG50 patient’s tumor tissues. Conclusion These data suggested that established lung cancer PDX models and primary cell lines reserved mostly molecular characteristics of primary lung cancer and could provide a new tool to further understand the mechanisms and explore new therapeutic strategies.

Details

Language :
English
ISSN :
14795876
Volume :
16
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Translational Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.579a6adb0438436d949cb2b90e57f8ea
Document Type :
article
Full Text :
https://doi.org/10.1186/s12967-018-1516-5