Background: Brain metastasis is a common complication among patients with lung cancer, yet the underlying mechanisms remain unclear. In this study, we aimed to investigate the pathogenesis of brain metastasis in lung cancer.
Methods: We established highly colonizing metastatic lung cancer cells, A549-M2, through multiple implantations of A549 human lung cancer cells in the carotid artery of athymic nude mice.
Results: Compared to parental cells (M0), M2 cells demonstrated slower growth in culture plates and soft agar, as well as lower motility and higher adhesion, key characteristics of mesenchymal-epithelial transition (MET). Further analysis revealed that M2 cells exhibited decreased expression of epithelial-mesenchymal transition markers, including ZEB1 and Vimentin. M2 cells also demonstrated reduced invasiveness in co-culture systems. RNA sequencing and gene set enrichment analysis confirmed that M2 cells underwent MET. Intriguingly, depletion of Noggin, a BMP antagonist, was observed in M2 cells, and replenishment of Noggin restored suppressed migration and invasion of M2 cells. In addition, Noggin knockdown in control M0 cells promoted cell attachment and suppressed cell migration, suggesting that Noggin reduction during brain colonization causes inhibition of migration and invasion of metastatic lung cancer cells.
Conclusions: Our results suggest that lung cancer cells undergo MET and lose their motility and invasiveness during brain metastatic colonization, which is dependent on Noggin.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683317 | PMC |
| http://dx.doi.org/10.1186/s12935-023-03155-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents.
J Med Chem
January 2025
Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, School of Pharmaceutical Sciences, Central University of Punjab, Bathinda 151 401, India.
The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.
View Article and Find Full Text PDFHigh-resolution national radon maps based on massive indoor measurements in the United States.
Proc Natl Acad Sci U S A
January 2025
Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02114.
Radon, a common radioactive indoor air pollutant, is the second leading cause of lung cancer in the United States. Knowledge about its distribution is essential for risk assessment and designing efficient protective regulations. However, the three current radon maps for the United States are unable to provide the up-to-date, high-resolution, and time-varying radon concentrations.
View Article and Find Full Text PDFPlant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity.
PLoS One
January 2025
Center of Excellence in Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand.
Anti-programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) have proven to be effective in treating various cancers, including colorectal, lung, and melanoma. Despite their clinical success, some patients develop resistance to mAbs, requiring co-treatments with radio- or chemotherapy. Interleukin-15 (IL-15) is an immunostimulatory cytokine that promotes immune cell production and proliferation.
View Article and Find Full Text PDFWDR62 mediates MAPK/ERK pathway to stimulate DNA damage repair and attenuate cisplatin sensitivity in lung adenocarcinoma.
Anticancer Drugs
January 2025
Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, China.
Chemotherapy resistance has long stood in the way of therapeutic advancement for lung cancer patients, the malignant tumor with the highest incidence and fatality rate in the world. Patients with lung adenocarcinoma (LUAD) now have a dismal prognosis due to the development of cisplatin (DDP) resistance, forcing them to use more costly second-line therapies. Therefore, overcoming resistance and enhancing patient outcomes can be achieved by comprehending the regulatory mechanisms of DDP resistance in LUAD.
View Article and Find Full Text PDFTRAIL agonists rescue mice from radiation-induced lung, skin or esophageal injury.
J Clin Invest
January 2025
Laboratory of Translational Oncology and Translational Cancer Therapeutics, Warren Alpert Medical School of Brown University, Providence, United States of America.
Radiotherapy can be limited by pneumonitis which is impacted by innate immunity, including pathways regulated by TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from toxic effects of radiation and found two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound (TIC10/ONC201) could reduce pneumonitis, alveolar-wall thickness, and oxygen desaturation. Lung protection extended to late effects of radiation including less fibrosis at 22-weeks in TLY012-rescued survivors versus un-rescued surviving irradiated-mice.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!