Interstitial flow influences direction of tumor cell migration through competing mechanisms
Open accessAbstract
Interstitial flow is the convective transport of fluid through tissue extracellular matrix. This creeping fluid flow has been shown to affect the morphology and migration of cells such as fibroblasts, cancer cells, endothelial cells, and mesenchymal stem cells. A microfluidic cell culture system was designed to apply stable pressure gradients and fluid flow and allow direct visualization of transient responses of cells seeded in a 3D collagen type I scaffold. We used this system to examine the effects of interstitial flow on cancer cell morphology and migration and to extend previous studies showing that interstitial flow increases the metastatic potential of MDA-MB-435S melanoma cells [Shields J, et al. (2007) Cancer Cell 11:526–538]. Using a breast carcinoma line (MDA-MB-231) we also observed cell migration along streamlines in the presence of flow; however, we further demonstrated that the strength of the flow as well as the cell density determined directional bias of migration along the streamline. In particular, we found that cells either at high seeding density or with the CCR-7 receptor inhibited migration against, rather than with the flow. We provide further evidence that CCR7-dependent autologous chemotaxis is the mechanism that leads to migration with the flow, but also demonstrate a competing CCR7-independent mechanism that causes migration against the flow. Data from experiments investigating the effects of cell concentration, interstitial flow rate, receptor activity, and focal adhesion kinase phosphorylation support our hypothesis that the competing stimulus is integrin mediated. This mechanism may play an important role in development of metastatic disease.
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Many aspects of cancer biology have been studied in microfluidic systems in which cancerous cells are cultured under well-controlled conditions.
“Many aspects of the biology of cancer have been studied in microfluidic systems in which cancerous cells (frequently co-cultured with non-cancerous cells) are cultured under well-controlled conditions [8,105,106,107,108].”
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 [105]
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- Authors
- Polacheck, W. J., Charest, J. L., & Kamm, R. D.
- Affiliations
- Massachusetts Institute of Technology (US)
- Draper Laboratory (US)
- Corresponding author
- Kamm, Roger D.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-06-20
- Volume
- 108
- Issue
- 27
- Pages
- 11115-11120
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3131352
- OpenAlex
- W1978496495
- Cited by
- 509
- References
- 1
- Citations by year
- 2026: 31 · 2025: 25 · 2024: 29 · 2023: 35 · 2022: 48 · 2021: 31 · 2020: 57 · 2019: 40 · 2018: 40 · 2017: 36 · 2016: 22 · 2015: 25 · 2014: 33 · 2013: 28 · 2012: 21
- FWCI
- 13.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Science Foundation
- Massachusetts Institute of Technology
- National Cancer Institute (R21CA140096)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- interstitial fluid flow, tumor cell migration, directional cell migration, CCR7, chemotaxis, breast cancer, MDA-MB-231 cells, melanoma, metastasis, cell density, integrin signaling, focal adhesion kinase, 3D collagen scaffold, microfluidic cell culture, pressure gradient
- MeSH terms
- Biomedical Engineering, Breast Neoplasms, Cell Count, Cell Movement, Chemotaxis, Female, Humans, Models, Biological, Neoplasm Metastasis, Signal Transduction, Finite Element Analysis, Extracellular Fluid, Cell Line, Tumor, Microfluidic Analytical Techniques, Focal Adhesion Kinase 1, Receptors, CCR7
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