SynthesisBMC cancer2014
Hypoxia increases membrane metallo-endopeptidase expression in a novel lung cancer ex vivo model - role of tumor stroma cells.
Synthesis in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Relevance of humanized three-dimensional tumor tissue models: a descriptive systematic literature review.Cellular and molecular life sciences : CMLS · 2020Pooled it
- From Local Tissue Repair to Fibrosis: Deciphering Gene Co-Expression Networks in Benign Pulmonary Nodules and Idiopathic Pulmonary Fibrosis Comorbidity via Bioinformatics and Machine Learning.International journal of molecular sciences · 2026Article
- Hypoxia-drives reversible cell cycle arrest in lung cancer cells via modulation of cellular redox and gene expression.Medical oncology (Northwood, London, England) · 2025Article
- Cryopreservation of human lung tissue for 3D ex vivo analysis.Respiratory research · 2025Review
- Defining hypoxia in cancer: A landmark evaluation of hypoxia gene expression signatures.Cell genomics · 2025Article
- TCAF2 in Pericytes Promotes Colorectal Cancer Liver Metastasis via Inhibiting Cold-Sensing TRPM8 Channel.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells.Frontiers in cell and developmental biology · 2023Article
- Chronic Inhalation Exposure to Antimony Trioxide Exacerbates the MAPK Signaling in Alveolar Bronchiolar Carcinomas in B6C3F1/N Mice.Toxicologic pathology · 2023Article
- Novel Stemness-Related Gene Signature Predicting Prognosis and Indicating a Different Immune Microenvironment in HNSCC.Frontiers in genetics · 2022Article
- Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition.Cell death discovery · 2021Article
- The evolving landscape of NMolecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- SARS-CoV-2/human interactome reveals ACE2 locus crosstalk with the immune regulatory network in the host.Pathogens and disease · 2021Article
- Repurposing of existing FDA approved drugs for Neprilysin inhibition: AnJournal of molecular structure · 2021Article
- Article
- From Donor to the Lab: A Fascinating Journey of Primary Cell Lines.Frontiers in cell and developmental biology · 2021Review
- Development and Validation of a Novel Hypoxia-Related Long Noncoding RNA Model With Regard to Prognosis and Immune Features in Breast Cancer.Frontiers in cell and developmental biology · 2021Article
- Identification and validation of hypoxia-derived gene signatures to predict clinical outcomes and therapeutic responses in stage I lung adenocarcinoma patients.Theranostics · 2021Article
- Monoacylglycerol lipase deficiency in the tumor microenvironment slows tumor growth in non-small cell lung cancer.Oncoimmunology · 2021Article
- Article
- Design strategy of optical probes for tumor hypoxia imaging.Science China. Life sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxia-induced genes are potential targets in cancer therapy. Responses to hypoxia have been extensively studied in vitro, however, they may differ in vivo due to the specific tumor microenvironment. In this study gene expression profiles were obtained from fresh human lung cancer tissue fragments cultured ex vivo under different oxygen concentrations in order to study responses to hypoxia in a model that mimics human lung cancer in vivo.
methodsNon-small cell lung cancer (NSCLC) fragments from altogether 70 patients were maintained ex vivo in normoxia or hypoxia in short-term culture. Viability, apoptosis rates and tissue hypoxia were assessed. Gene expression profiles were studied using Affymetrix GeneChip 1.0 ST microarrays.
resultsApoptosis rates were comparable in normoxia and hypoxia despite different oxygenation levels, suggesting adaptation of tumor cells to hypoxia. Gene expression profiles in hypoxic compared to normoxic fragments largely overlapped with published hypoxia-signatures. While most of these genes were up-regulated by hypoxia also in NSCLC cell lines, membrane metallo-endopeptidase (MME, neprilysin, CD10) expression was not increased in hypoxia in NSCLC cell lines, but in carcinoma-associated fibroblasts isolated from non-small cell lung cancers. High MME expression was significantly associated with poor overall survival in 342 NSCLC patients in a meta-analysis of published microarray datasets.
conclusionsThe novel ex vivo model allowed for the first time to analyze hypoxia-regulated gene expression in preserved human lung cancer tissue. Gene expression profiles in human hypoxic lung cancer tissue overlapped with hypoxia-signatures from cancer cell lines, however, the elastase MME was identified as a novel hypoxia-induced gene in lung cancer. Due to the lack of hypoxia effects on MME expression in NSCLC cell lines in contrast to carcinoma-associated fibroblasts, a direct up-regulation of stroma fibroblast MME expression under hypoxia might contribute to enhanced aggressiveness of hypoxic cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.