Interstitial fluid pressure regulates collective invasion in engineered human breast tumors via Snail, vimentin, and E-cadherin
Open accessAbstract
Many solid tumors exhibit elevated interstitial fluid pressure (IFP). This elevated pressure within the core of the tumor results in outward flow of interstitial fluid to the tumor periphery. We previously found that the directionality of IFP gradients modulates collective invasion from the surface of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. Here, we used this 3D engineered tumor model to investigate the molecular mechanisms underlying IFP-induced changes in invasive phenotype. We found that IFP alters the expression of genes associated with epithelial-mesenchymal transition (EMT). Specifically, the levels of Snail, vimentin, and E-cadherin were increased under pressure conditions that promoted collective invasion. These changes in gene expression were sufficient to direct collective invasion in response to IFP. Furthermore, we found that IFP modulates the motility and persistence of individual cells within the aggregates, which are also influenced by the expression levels of EMT markers. Together, these data provide insight into the molecular mechanisms that guide collective invasion from primary tumors in response to IFP.
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When pressure at the base (Pbase) was higher than pressure at the tip (Ptip), an invasive phenotype was favored.
“For example, when Pbase was higher than Ptip, an invasive phenotype was favored”
From The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors (2019) · cites this paper as [30]
The Results section reports the opposite: when Pbase>Ptip, none of 51 aggregates developed invasions. Invasion was promoted when Pbase<Ptip, with 50% of aggregates developing invasions. Page numbers were not provided in the supplied passages. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredMost research is focused on how IFP prompts cancer cell migration and metastasis.
“Most research is focused on how IFP prompts cancer cells migration and metastasis [157,[167][168][169].”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [167]
The Introduction (page unavailable) describes several studies of how IFP and interstitial flow affect cancer-cell migration, and the paper investigates migration and invasion. The Discussion (page unavailable) mentions metastasis only as a potential consequence; it does not establish that most research focuses on migration and metastasis or that IFP prompts metastasis. (LLM, conf=0.83)
Experimental — accuracy not yet measuredEven simple pressure gradients were able to induce distinct invasiveness behaviors in tumor cells embedded in collagen.
“The authors observed that even simple pressure gradients were able to induce distinct invasiveness behaviors.”
From The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors (2019) · cites this paper as [30]
15 ligand-receptor pairs were identified to be related to the chemotactic invasion of GSCs toward the perivascular niche.
“Using single‐cell RNA sequencing, 15 ligand–receptor pairs were identified to be related to the chemotactic invasion of GSCs toward the perivascular niche.”
From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [155]
The Results section on cell motility examines engineered human breast-tumor aggregates under interstitial fluid-pressure gradients. Searches for single-cell RNA sequencing, GSCs, the perivascular niche, and 15 ligand–receptor pairs found no passage in our copy addressing the claimed finding. (LLM, conf=0.77)
Experimental — accuracy not yet measured
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- Authors
- Piotrowski-Daspit, A. S., Tien, J., & Nelson, C. M.
- Affiliations
- Princeton University (US)
- Boston University (US)
- Corresponding author
- Nelson, Celeste M.
- Venue
- Integrative Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-02-08
- Volume
- 8
- Issue
- 3
- Pages
- 319-331
- ISSN
- 1757-9694 (ISSN-L)
- 1757-9708
- PMC
- PMC4792648
- OpenAlex
- W2270658878
- Semantic Scholar
- 54829dce3c19c7e4f22cca06c4cfffd4e6cb53b1
- Cited by
- 101
- References
- 56
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 12 · 2023: 9 · 2022: 8 · 2021: 11 · 2020: 18 · 2019: 13 · 2018: 8 · 2017: 8 · 2016: 3
- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Integrative Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL110335, HL118532, HL120142)
- Burroughs Wellcome Fund (Unassigned)
- National Cancer Institute (CA143803, CA187692)
- National Institute of General Medical Sciences (GM08997)
- Congressionally Directed Medical Research Programs (W81XWH-09-1-0565)
- Alfred P. Sloan Foundation (Unassigned)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- interstitial fluid pressure, collective invasion, breast cancer, epithelial-mesenchymal transition, snails, vimentin, E-cadherin, MDA-MB-231 cells, tumor microenvironment, cell motility, cell persistence
- MeSH terms
- Snail Family Transcription Factors, Breast Neoplasms, Cell Aggregation, Cell Movement, Female, Humans, Neoplasm Invasiveness, Vimentin, Cadherins, Spheroids, Cellular, Coculture Techniques, RNA, Small Interfering, Extracellular Fluid, Cell Line, Tumor, Epithelial-Mesenchymal Transition, Cell Engineering
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