Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines

Abstract Lung cancer is a leading cause of cancer-related deaths worldwide, with brain metastasis occurring in approximately 30–55% of patients, particularly in lung adenocarcinoma. Due to the challenges in obtaining genuine brain metastasis tumor cells, researchers commonly use nude mouse models to...

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Main Authors: Jintao He, Zen-ichi Tanei, Dao-Sian Wu, Lei Wang, Yoshitaka Oda, Masumi Tsuda, Shinya Tanaka
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Acta Neuropathologica Communications
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Online Access:https://doi.org/10.1186/s40478-025-02038-4
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author Jintao He
Zen-ichi Tanei
Dao-Sian Wu
Lei Wang
Yoshitaka Oda
Masumi Tsuda
Shinya Tanaka
author_facet Jintao He
Zen-ichi Tanei
Dao-Sian Wu
Lei Wang
Yoshitaka Oda
Masumi Tsuda
Shinya Tanaka
author_sort Jintao He
collection DOAJ
description Abstract Lung cancer is a leading cause of cancer-related deaths worldwide, with brain metastasis occurring in approximately 30–55% of patients, particularly in lung adenocarcinoma. Due to the challenges in obtaining genuine brain metastasis tumor cells, researchers commonly use nude mouse models to establish brain metastasis cell lines, though traditional methods have limitations such as high costs, lengthy timeframes, and the need for specialized imaging equipment. To address these issues, we developed an improved approach by performing low cell number circulating intracranial injections (500–4000 cells) in nude mice, successfully establishing the H1975-BM1, BM2, and BM3 cell lines. Through RNA sequencing and bioinformatics analyses, we identified transcriptomic differences among these cell lines, revealing that H1975-BM1 cells primarily exhibit stem cell function and migration characteristics, while H1975-BM3 cells display enhanced chemotaxis, cell adhesion, and cytokine secretion associated with interactions. Experimental validation, including Transwell assays, CCK8, cell adhesion assays, and subcutaneous tumor implantation in nude mice, further confirmed these findings, with H1975-BM3 forming larger tumors and a more pronounced secretion cystic cavity. In conclusion, our improved methodology successfully established high-confidence brain metastasis lung adenocarcinoma cell lines, elucidating distinct transcriptomic and functional characteristics at different stages of brain metastasis progression.
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publishDate 2025-05-01
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spelling doaj-art-cfd25f6695ad42828c2ce30e15f5e6b22025-08-20T02:29:46ZengBMCActa Neuropathologica Communications2051-59602025-05-0113111610.1186/s40478-025-02038-4Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell linesJintao He0Zen-ichi Tanei1Dao-Sian Wu2Lei Wang3Yoshitaka Oda4Masumi Tsuda5Shinya Tanaka6Department of Cancer Pathology, Faculty of Medicine, Hokkaido UniversityDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido UniversitySchool of Medicine, College of Medicine, Taipei Medical UniversityDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido UniversityDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido UniversityDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido UniversityDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido UniversityAbstract Lung cancer is a leading cause of cancer-related deaths worldwide, with brain metastasis occurring in approximately 30–55% of patients, particularly in lung adenocarcinoma. Due to the challenges in obtaining genuine brain metastasis tumor cells, researchers commonly use nude mouse models to establish brain metastasis cell lines, though traditional methods have limitations such as high costs, lengthy timeframes, and the need for specialized imaging equipment. To address these issues, we developed an improved approach by performing low cell number circulating intracranial injections (500–4000 cells) in nude mice, successfully establishing the H1975-BM1, BM2, and BM3 cell lines. Through RNA sequencing and bioinformatics analyses, we identified transcriptomic differences among these cell lines, revealing that H1975-BM1 cells primarily exhibit stem cell function and migration characteristics, while H1975-BM3 cells display enhanced chemotaxis, cell adhesion, and cytokine secretion associated with interactions. Experimental validation, including Transwell assays, CCK8, cell adhesion assays, and subcutaneous tumor implantation in nude mice, further confirmed these findings, with H1975-BM3 forming larger tumors and a more pronounced secretion cystic cavity. In conclusion, our improved methodology successfully established high-confidence brain metastasis lung adenocarcinoma cell lines, elucidating distinct transcriptomic and functional characteristics at different stages of brain metastasis progression.https://doi.org/10.1186/s40478-025-02038-4Lung adenocarcinomaBrain metastasisCell linesTranscriptomic analysis
spellingShingle Jintao He
Zen-ichi Tanei
Dao-Sian Wu
Lei Wang
Yoshitaka Oda
Masumi Tsuda
Shinya Tanaka
Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines
Acta Neuropathologica Communications
Lung adenocarcinoma
Brain metastasis
Cell lines
Transcriptomic analysis
title Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines
title_full Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines
title_fullStr Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines
title_full_unstemmed Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines
title_short Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines
title_sort distinct characteristics of brain metastasis in lung adenocarcinoma development of high confidence cell lines
topic Lung adenocarcinoma
Brain metastasis
Cell lines
Transcriptomic analysis
url https://doi.org/10.1186/s40478-025-02038-4
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