The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.
Leading malignant cells initiate collective epithelial cell invasion in a three-dimensional heterotypic tumor spheroid model
Open accessAbstract
Solid tumors consist of genetically and phenotypically diverse subpopulations of cancer cells with unique capacities for growth, differentiation, and invasion. While the molecular and microenvironmental bases for heterogeneity are increasingly appreciated, the outcomes of such intratumor heterogeneity, particularly in the context of tumor invasion and metastasis, remain poorly understood. To study heterotypic cell-cell interactions and elucidate the biological consequences of intratumor heterogeneity, we developed a tissue-engineered multicellular spheroid (MCS) co-culture model that recapitulates the cellular diversity and fully three-dimensional cell-cell and cell-matrix interactions that characterize human carcinomas. We found that "invasion-competent" malignant cells induced the collective invasion of otherwise "invasion-incompetent" epithelial cells, and that these two cell types consistently exhibited distinct leader and follower roles during invasion. Analysis of extracellular matrix (ECM) microarchitecture revealed that malignant cell invasion was accompanied by extensive ECM remodeling including matrix alignment and proteolytic track-making. Inhibition of cell contractility- and proteolysis-mediated matrix reorganization prevented leader-follower behavior and malignant cell-induced epithelial cell invasion. These results indicate that heterogeneous subpopulations within a tumor may possess specialized roles during tumor progression and suggest that complex interactions among the various subpopulations of cancer cells within a tumor may regulate critical aspects of tumor biology and affect clinical outcome.
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“it was recently demonstrated that alignment directs tumor invasion in hydrogels containing anisotropic structures”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [29]
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Metadata
- Authors
- Carey, S. P., Starchenko, A., McGregor, A. L., & Reinhart-King, C. A.
- Affiliations
- Cornell University (US)
- ORCID
- Starchenko, Alina
- Venue
- Clinical & Experimental Metastasis
- Published
- 2013-01-18
- Volume
- 30
- Issue
- 5
- Pages
- 615-630
- ISSN
- 0262-0898 (ISSN-L)
- 1573-7276
- PMC
- PMC3646083
- OpenAlex
- W2143947514
- Cited by
- 174
- References
- 81
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 13 · 2023: 16 · 2022: 12 · 2021: 12 · 2020: 12 · 2019: 18 · 2018: 15 · 2017: 16 · 2016: 18 · 2015: 8 · 2014: 7 · 2013: 5
- FWCI
- 6.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Clinical & Experimental Metastasis (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- Barbara Ann Karmanos Cancer Institute
- National Cancer Institute (U54CA143876)
- Division of Civil, Mechanical and Manufacturing Innovation
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- intratumoral heterogeneity, collective cell invasion, leader-follower behavior, cancer cells, epithelial cells, tumor spheroids, extracellular matrix remodeling, proteolysis, cell contractility, cell-matrix interactions, tumor progression, metastasis
- MeSH terms
- Epithelial Cells, Extracellular Matrix, Female, Humans, Models, Biological, Neoplasm Invasiveness, Spheroids, Cellular, Cell Line, Tumor, Tumor Microenvironment
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