Cited by 1,483Cell Adhesion Molecules ResearchCellular Mechanics and InteractionsCancer Cells and Metastasis

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Reversion of the Malignant Phenotype of Human Breast Cells in Three-Dimensional Culture and In Vivo by Integrin Blocking Antibodies

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Weaver, V.M., Petersen, O.W., Wang, F., Larabell, C.A., Briand, P., Damsky, C., Bissell, M.J.·1997·The Journal of Cell Biology

DOI 10.1083/jcb.137.1.231PMC PMC2139858

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Abstract

In a recently developed human breast cancer model, treatment of tumor cells in a 3-dimensional culture with inhibitory β1-integrin antibody or its Fab fragments led to a striking morphological and functional reversion to a normal phenotype. A stimulatory β1-integrin antibody proved to be ineffective. The newly formed reverted acini re-assembled a basement membrane and re-established E-cadherin–catenin complexes, and re-organized their cytoskeletons. At the same time they downregulated cyclin D1, upregulated p21cip,waf-1, and stopped growing. Tumor cells treated with the same antibody and injected into nude mice had significantly reduced number and size of tumors in nude mice. The tissue distribution of other integrins was also normalized, suggesting the existence of intimate interactions between the different integrin pathways as well as adherens junctions. On the other hand, nonmalignant cells when treated with either α6 or β4 function altering antibodies continued to grow, and had disorganized colony morphologies resembling the untreated tumor colonies. This shows a significant role of the α6/β4 heterodimer in directing polarity and tissue structure. The observed phenotypes were reversible when the cells were disassociated and the antibodies removed. Our results illustrate that the extracellular matrix and its receptors dictate the phenotype of mammary epithelial cells, and thus in this model system the tissue phenotype is dominant over the cellular genotype.

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Authors: Weaver, V. M., Petersen, O. W., Wang, F., Larabell, C. A., Briand, P., Damsky, C., & Bissell, M. J.
Affiliations: Lawrence Berkeley National Laboratory (US)
Corresponding author: Weaver, V.M.
ORCID: Weaver, V.M.
Venue: The Journal of Cell Biology
Publisher: Rockefeller University Press
Published: 1997-04-07
Volume: 137
Issue: 1
Pages: 231-245
ISSN: 0021-9525 (ISSN-L)
1540-8140
DOI: 10.1083/jcb.137.1.231
PMC: PMC2139858
OpenAlex: W1541555963
Cited by: 1,483
References: 98
Citations by year: 2026: 19 · 2025: 27 · 2024: 19 · 2023: 51 · 2022: 38 · 2021: 49 · 2020: 50 · 2019: 51 · 2018: 62 · 2017: 63 · 2016: 63 · 2015: 58 · 2014: 64 · 2013: 63 · 2012: 89
FWCI: 13.87
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Cell Biology (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
University of North Texas Digital Library (University of North Texas) (submittedVersion)
OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Lawrence Berkeley National Laboratory
Funders: U.S. Department of Defense (DE-AC02-05CH11231)
U.S. Department of Energy (-AC02-05CH11231, DE-AC03-?, 05CH11231, DE AC02 05CH11231, DE-AC03-SF00098, DE-AC02-)
Sundhed og Sygdom, Det Frie Forskningsråd
National Institutes of Health (DE-AC02–05CH11231)
Medical Research Council (DE-AC02-05CH11231)
National Cancer Institute (CA-64786, R37CA064786, R01CA064786)
Lawrence Berkeley National Laboratory (AC02‐05CH11231, DE-AC02-05CH11231, 05CH11231)
Topics: Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: beta1 integrin, integrin blocking antibodies, breast cancer, 3D cell culture, E-cadherin-catenin complex, adherens junctions, extracellular matrix, mammary epithelial cells, cyclin D1, p21, tumor growth inhibition, cell polarity, tissue structure
MeSH terms: Animals, Antibodies, Monoclonal, Basement Membrane, Binding, Competitive, Breast Neoplasms, Cell Division, Extracellular Matrix, Female, Fluorescent Antibody Technique, Genotype, Humans, Immunoglobulin Fab Fragments, Phenotype, Transformation, Genetic, Tumor Cells, Cultured, Signal Transduction, Antigens, CD, Integrin beta1, Integrin beta4, Mice, Rats

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Reversion of the Malignant Phenotype of Human Breast Cells in Three-Dimensional Culture and In Vivo by Integrin Blocking Antibodies

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