ArticleCell death & disease2017
Three-dimensional tumor cell growth stimulates autophagic flux and recapitulates chemotherapy resistance.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
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- In vitro studies of human erythropoiesis using a 3D silk-based bone marrow model that generates erythroblastic islands.Blood advances · 2025Article
- Mimicking the Complexity of Solid Tumors: How Spheroids Could Advance Cancer Preclinical Transformative Approaches.Cancers · 2025Article
- AMPK Knockout Impairs the Formation of Three-Dimensional Spheroids.Life (Basel, Switzerland) · 2025Article
- Integrating bioengineering, super-resolution microscopy and mechanobiology in autophagy research: addendum to the guidelines (4th edition).Autophagy · 2025Article
- Principles of Hanging Drop Method (Spheroid Formation) in Cell Culture.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Synergy of retinoic acid and BH3 mimetics in MYC(N)-driven embryonal nervous system tumours.British journal of cancer · 2024Article
- Pentoxifylline and Norcantharidin Modify p62 Expression in 2D and 3D Cultures of B16F1 Cells.International journal of molecular sciences · 2024Article
- Modular synthesis of functional libraries by accelerated SuFEx click chemistry.Chemical science · 2024Article
- Evaluating the RIST Molecular-Targeted Regimen in a Three-Dimensional Neuroblastoma Spheroid Cell Culture Model.Cancers · 2023Article
- Reflections on the Biology of Cell Culture Models: Living on the Edge of Oxidative Metabolism in Cancer Cells.International journal of molecular sciences · 2023Review
- Technical report: liquid overlay technique allows the generation of homogeneous osteosarcoma, glioblastoma, lung and prostate adenocarcinoma spheroids that can be used for drug cytotoxicity measurements.Frontiers in bioengineering and biotechnology · 2023Article
- Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM.NPJ precision oncology · 2022Article
- Three-dimensional in vitro culture models in oncology research.Cell & bioscience · 2022Review
- MatriGridBioengineering (Basel, Switzerland) · 2022Review
- Metabolic Reprogramming and Lipophagy Mediates Survival of Ascites Derived Metastatic Ovarian Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g., via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions. Here we show that both static 3D growth and 3D growth within a bioreactor system modulate key hallmarks of cancer cells, including proliferation and cell death as well as macroautophagy, a recycling pathway often activated by highly proliferative tumors to cope with metabolic stress. The autophagy-related gene expression profiles of 2D-grown cells are substantially different from those of 3D-grown cells and tumor tissue. Autophagy-controlling transcription factors, such as TFEB and FOXO3, are upregulated in tumors, and 3D-grown cells have increased expression compared with cells grown in 2D conditions. Three-dimensional cultures depleted of the autophagy mediators BECN1, ATG5 or ATG7 or the transcription factor FOXO3, are more sensitive to cytotoxic treatment. Accordingly, combining cytotoxic treatment with compounds affecting late autophagic flux, such as chloroquine, renders the 3D-grown cells more susceptible to therapy. Altogether, 3D cultures are a valuable tool to study drug response of tumor cells, as these models more closely mimic tumor (patho-)physiology, including the upregulation of tumor relevant pathways, such as autophagy.
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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.