The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Micro-Environmental Mechanical Stress Controls Tumor Spheroid Size and Morphology by Suppressing Proliferation and Inducing Apoptosis in Cancer Cells
Open accessAbstract
BACKGROUND: Compressive mechanical stress produced during growth in a confining matrix limits the size of tumor spheroids, but little is known about the dynamics of stress accumulation, how the stress affects cancer cell phenotype, or the molecular pathways involved. METHODOLOGY/PRINCIPAL FINDINGS: We co-embedded single cancer cells with fluorescent micro-beads in agarose gels and, using confocal microscopy, recorded the 3D distribution of micro-beads surrounding growing spheroids. The change in micro-bead density was then converted to strain in the gel, from which we estimated the spatial distribution of compressive stress around the spheroids. We found a strong correlation between the peri-spheroid solid stress distribution and spheroid shape, a result of the suppression of cell proliferation and induction of apoptotic cell death in regions of high mechanical stress. By compressing spheroids consisting of cancer cells overexpressing anti-apoptotic genes, we demonstrate that mechanical stress-induced apoptosis occurs via the mitochondrial pathway. CONCLUSIONS/SIGNIFICANCE: Our results provide detailed, quantitative insight into the role of micro-environmental mechanical stress in tumor spheroid growth dynamics, and suggest how tumors grow in confined locations where the level of solid stress becomes high. An important implication is that apoptosis via the mitochondrial pathway, induced by compressive stress, may be involved in tumor dormancy, in which tumor growth is held in check by a balance of apoptosis and proliferation.
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Cites
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Cited by
Role of Extracellular Matrix in Development and Cancer Progression
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Self-citationCauses, consequences, and remedies for growth-induced solid stress in murine and human tumors
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Mechanical compression drives cancer cells toward invasive phenotype
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Metadata
- Authors
- Cheng, G., Tse, J., Jain, R. K., & Munn, L. L.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-02-27
- Volume
- 4
- Issue
- 2
- Pages
- e4632
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2146839980
- Cited by
- 478
- References
- 23
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- gold
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