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Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation
Open accessAbstract
Significance: The cancer biology seed-and-soil paradigm recognizes the existence of organ-specific patterns of metastasization that drive the spread of selected primary tumors toward specific secondary loci. However, despite efforts to model the organotypic microenvironment, the organ specificity of cancer metastases needs to be elucidated. The relevance of this study lies in the generation of a human vascularized organ-specific microenvironment, which can be used to investigate and tune the extravasation process of metastatic tumor cells. Furthermore, beyond mimicking the pro- or antimetastatic signatures of different microenvironments, our microfluidic model provides insights into different properties of organ-specific endothelia. This study paves the way toward advanced in vitro models to screen for highly tailored organ-specific therapeutics and investigate key molecular pathways involved in organ-specific metastases.
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“Through this, it was shown that adenosine played an important role in promoting tumor cells extravasation.”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [98]
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“By blocking A3 adenosine receptors, cancer cells were observed to have a reduced extravasation rate.”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [98]
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“Endothelial cells displayed morphological features similar to in vivo conditions, contrasting to poorly aligned cells grown in 2D cultures or deprived of fl ow.”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [78]
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“This micro fl uidic device not only promoted the perfusable culture of four different cells types but also proved to be an appropriate platform for monitoring cancer cell extravasation in real time.”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [78]
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“The results indicated inhibitory role of adenosine on extravasation as blocking A3 adenosine receptors increased extravasation rates of breast cancer cells into the myoblast, mimicking microenvironments compared with untreated cells [57].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [57]
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“Fortunately, with the development of biofabrication techniques, microfluidic and 3D bioprinting technologies have been employed to create more in vivo‐like perfusable 3D tumor models in the biomimetic matrix.[ 72 , 161 ]”
From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [161]
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“CoC models can be applied to elucidate these effects, and researchers have developed vascularized CoC models to study extravasation to bone [74][75][76], brain [77,78], and other organs [79]”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [75]
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Metadata
- Authors
- Jeon, J. S., Bersini, S., Gilardi, M., Dubini, G., Charest, J. L., Moretti, M., & Kamm, R. D.
- Affiliations
- Massachusetts Institute of Technology (US)
- IRCCS Ospedale Galeazzi - Sant'Ambrogio (IT)
- Politecnico di Milano (IT)
- Draper Laboratory (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-12-18
- Volume
- 112
- Issue
- 1
- Pages
- 214-219
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4291627
- OpenAlex
- W2081560083
- Semantic Scholar
- f475569e9cefbccc34378d56e185a60e479f18b8
- Cited by
- 723
- References
- 44
- Citations by year
- 2026: 28 · 2025: 44 · 2024: 53 · 2023: 71 · 2022: 79 · 2021: 85 · 2020: 83 · 2019: 71 · 2018: 77 · 2017: 59 · 2016: 52 · 2015: 21
- FWCI
- 22.85
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-02-02)
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Virtual Community of Pathological Anatomy (University of Castilla La Mancha) (submittedVersion, other-oa)
- BOA (University of Milano-Bicocca) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- HHS | NIH | National Cancer Institute (R33 CA174550-01, R21 CA140096)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- breast cancer, tumor cell extravasation, organ-specific metastasis, microvascular permeability, A3 adenosine receptor, drug screening, personalized medicine
- MeSH terms
- Adenosine, Animals, Breast Neoplasms, Capillary Permeability, Extravasation of Diagnostic and Therapeutic Materials, Female, Humans, Stress, Mechanical, Shear Strength, Microfluidics, Cell Line, Tumor, Mice, Microvessels, Cellular Microenvironment, Human Umbilical Vein Endothelial Cells
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