ArticleJournal of the National Cancer Institute2002
Phenotypic reversion or death of cancer cells by altering signaling pathways in three-dimensional contexts.
Article in Journal of the National Cancer Institute, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
142 citing papers in PubMed, 266 citations in OpenAlex.
- Development of a 3D-bioprinted tumour-on-chip with tunable hydrogel properties for monitoring colorectal cancer cell migration and invasion.Materials today. Bio · 2026Article
- Prediction of Patient Drug Response via 3D Bioprinted Gastric Cancer Model Utilized Patient-Derived Tissue Laden Tissue-Specific Bioink.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Spheroid Model of Mammary Tumor Cells: Epithelial-Mesenchymal Transition and Doxorubicin Response.Biology · 2024Article
- The Role of β1 Integrin/CD29 as a Potential Prognostic Factor for the Risk of Progression to Cervical Carcinoma in HPV-Associated Lesions.Medicina (Kaunas, Lithuania) · 2024Article
- Ligand-independent integrin β1 signaling supports lung adenocarcinoma development.JCI insight · 2022Article
- Glucose-limiting conditions induce an invasive population of MDA-MB-231 breast cancer cells with increased connexin 43 expression and membrane localization.Journal of cell communication and signaling · 2021Article
- Tumor reversion: a dream or a reality.Biomarker research · 2021Review
- Interplay between aging, lung inflammation/remodeling, and fibronectin EDA in lung cancer progression.Cancer biology & therapy · 2020Article
- The not-so-sweet side of sugar: Influence of the microenvironment on the processes that unleash cancer.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Review
- Lung-resident mesenchymal stromal cells are tissue-specific regulators of lung homeostasis.American journal of physiology. Lung cellular and molecular physiology · 2020Review
- Elevated leptin disrupts epithelial polarity and promotes premalignant alterations in the mammary gland.Oncogene · 2019Article
- Dissecting the Dual Nature of Hyaluronan in the Tumor Microenvironment.Frontiers in immunology · 2019Review
- A Functionally Robust Phenotypic Screen that Identifies Drug Resistance-associated Genes Using 3D Cell Culture.Bio-protocol · 2018Article
- Dormant tumour cells, their niches and the influence of immunity.Nature cell biology · 2018Review
- Article
- A new cell-laden 3D Alginate-Matrigel hydrogel resembles human breast cancer cell malignant morphology, spread and invasion capability observed "in vivo".Scientific reports · 2018Article
- Sleeping Beauty and the Microenvironment Enchantment: Microenvironmental Regulation of the Proliferation-Quiescence Decision in Normal Tissues and in Cancer Development.Frontiers in cell and developmental biology · 2018Review
- Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression.Frontiers in cell and developmental biology · 2018Review
- Advances in the development of improved animal-free models for use in breast cancer biomedical research.Biophysical reviews · 2017Review
82 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundWe previously used a three-dimensional (3D) reconstituted basement membrane (rBM) assay to demonstrate that tumorigenic HMT-3522 T4-2 human breast cells can be induced to form morphologically normal structures ("reversion") by treatment with inhibitors of beta1 integrin, the epidermal growth factor receptor (EGFR), or mitogen-activated protein kinase (MAPK). We have now used this assay to identify reversion and/or death requirements of several more aggressive human breast cancer cell lines.
methodsBreast tumor cell lines MCF7, Hs578T, and MDA-MB-231 were cultured in 3D rBM and treated with inhibitors of beta1 integrin, MAPK, or phosphatidylinositol 3-kinase (PI3K). MDA-MB-231 cells, which lack E-cadherin, were transfected with an E-cadherin cDNA. The extent of reversion was assessed by changes in morphology and polarity, growth in 3D rBM or soft agar, level of invasiveness, and tumor formation in nude mice.
resultsAll three cell lines showed partial reversion (MCF7 the greatest and Hs578T the least) of tumorigenic properties treated with a single beta1 integrin, MAPK, or PI3K inhibitor. Combined inhibition of beta1 integrin and either PI3K or MAPK resulted in nearly complete phenotypic reversion (MDA-MB-231, MCF7) or in cell death (Hs578T). E-cadherin-transfected MDA-MB-231 cells showed partial reversion, but exposure of the transfectants to an inhibitor of beta1 integrin, PI3K, or MAPK led to nearly complete reversion.
conclusionThe 3D rBM assay can be used to identify signaling pathways that, when manipulated in concert, can lead to the restoration of morphologically normal breast structures or to death of the tumor cells, even highly metastatic cells. This approach may be useful to design therapeutic intervention strategies for aggressive breast cancers.
Indexed as
Identifiers
What OpenQuestion holds
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.