ArticleProceedings of the National Academy of Sciences of the United States of America2012
Host epithelial geometry regulates breast cancer cell invasiveness.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 77 citations in OpenAlex.
- Article
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- Spatial Engineering of Mammary Epithelial Cell Cultures with 3D Bioprinting Reveals Growth Control by Branch Point Proximity.Journal of mammary gland biology and neoplasia · 2024Article
- Entropy as a Geometrical Source of Information in Biological Organizations.Entropy (Basel, Switzerland) · 2022Article
- Intrinsic cell rheology drives junction maturation.Nature communications · 2022Article
- Aligned forces: Origins and mechanisms of cancer dissemination guided by extracellular matrix architecture.Current opinion in cell biology · 2021Review
- Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?Journal of mammary gland biology and neoplasia · 2021Review
- Peritumoral edema in breast cancer at preoperative MRI: an interpretative study with histopathological review toward understanding tumor microenvironment.Scientific reports · 2021Article
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- Three-dimensional microscale hanging drop arrays with geometric control for drug screening and live tissue imaging.Science advances · 2021Article
- The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems.Cell communication and signaling : CCS · 2021Review
- 3D Cell Culture for the Study of Microenvironment-Mediated Mechanostimuli to the Cell Nucleus: An Important Step for Cancer Research.Frontiers in molecular biosciences · 2021Article
- Recapitulating TumorigenesisFrontiers in bioengineering and biotechnology · 2021Review
- Geometric Dependence of 3D Collective Cancer Invasion.Biophysical journal · 2020Article
- Article
- Coupling synthetic biology and programmable materials to construct complex tissue ecosystems.MRS communications · 2019Article
- Dispersible hydrogel force sensors reveal patterns of solid mechanical stress in multicellular spheroid cultures.Nature communications · 2019Article
- Cell-Cell Adhesion and Cortical Actin Bending Govern Cell Elongation on Negatively Curved Substrates.Biophysical journal · 2018Article
- Microfabrication-Based Three-Dimensional (3-D) Extracellular Matrix Microenvironments for Cancer and Other Diseases.International journal of molecular sciences · 2018Review
- Multicellular tumor invasion and plasticity in biomimetic materials.Biomaterials science · 2017Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Breast tumor development is regulated in part by cues from the local microenvironment, including interactions with neighboring nontumor cells as well as the ECM. Studies using homogeneous populations of breast cancer cell lines cultured in 3D ECM have shown that increased ECM stiffness stimulates tumor cell invasion. However, at early stages of breast cancer development, malignant cells are surrounded by normal epithelial cells, which have been shown to exert a tumor-suppressive effect on cocultured cancer cells. Here we explored how the biophysical characteristics of the host microenvironment affect the proliferative and invasive tumor phenotype of the earliest stages of tumor development, by using a 3D microfabrication-based approach to engineer ducts composed of normal mammary epithelial cells that contained a single tumor cell. We found that the phenotype of the tumor cell was dictated by its position in the duct: proliferation and invasion were enhanced at the ends and blocked when the tumor cell was located elsewhere within the tissue. Regions of invasion correlated with high endogenous mechanical stress, as shown by finite element modeling and bead displacement experiments, and modulating the contractility of the host epithelium controlled the subsequent invasion of tumor cells. Combining microcomputed tomographic analysis with finite element modeling suggested that predicted regions of high mechanical stress correspond to regions of tumor formation in vivo. This work suggests that the mechanical tone of nontumorigenic host epithelium directs the phenotype of tumor cells and provides additional insight into the instructive role of the mechanical tumor microenvironment.
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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.