Stress clamp experiments on multicellular tumor spheroids.

The precise role of the microenvironment on tumor growth is poorly understood. Whereas the tumor is in constant competition with the surrounding tissue, little is known about the mechanics of this interaction. Using a novel experimental procedure, we study quantitatively the effect of an applied mechanical stress on the long-term growth of a spheroid cell aggregate. We observe that a stress of 10 kPa is sufficient to drastically reduce growth by inhibition of cell proliferation mainly in the core of the spheroid. We compare the results to a simple numerical model developed to describe the role of mechanics in cancer progression.

[1]  Journal of Biotechnology , 2022 .

[2]  B. Cabane,et al.  Osmotic pressure of latex dispersions , 1994 .

[3]  E. Hoffmann,et al.  Effects of osmotic stress on the activity of MAPKs and PDGFR-beta-mediated signal transduction in NIH-3T3 fibroblasts. , 2008, American journal of physiology. Cell physiology.

[4]  J. L. Gould,et al.  The Quarterly Review of Biology , 2005, The Quarterly Review of Biology.

[5]  W. Mueller‐Klieser.  Three-dimensional cell cultures: from molecular mechanisms to clinical applications. , 1997, American journal of physiology. Cell physiology.

[6]  S. Lowen.  The Biophysical Journal , 1960, Nature.

[7]  E. Hall,et al.  The nature of biotechnology. , 1988, Journal of biomedical engineering.

[8]  K. Storey,et al.  Mitogen-activated protein kinases: new signaling pathways functioning in cellular responses to environmental stress , 2003, Journal of Experimental Biology.

[9]  Gernot Schaller,et al.  Multicellular tumor spheroid in an off-lattice Voronoi-Delaunay cell model. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[10]  Emmanuel Farge,et al.  Mechanical factors activate ß‐catenin‐dependent oncogene expression in APC1638N/+ mouse colon , 2008, HFSP journal.

[11]  F. Gallyas,et al.  Hyperosmotic stress-induced apoptotic signaling pathways in chondrocytes. , 2007, Bone.

[12]  R. Jain,et al.  Micro-Environmental Mechanical Stress Controls Tumor Spheroid Size and Morphology by Suppressing Proliferation and Inducing Apoptosis in Cancer Cells , 2009, PloS one.

[13]  L. Bertalanffy.  Quantitative Laws in Metabolism and Growth , 1957 .

[14]  Jacques Prost,et al.  Homeostatic competition drives tumor growth and metastasis nucleation , 2009, HFSP journal.

[15]  J. Jardin,et al.  Casein micelle dispersions under osmotic stress. , 2009, Biophysical journal.

[16]  L. Kunz-Schughart,et al.  Multicellular tumor spheroids: an underestimated tool is catching up again. , 2010, Journal of biotechnology.

[17]  E. Kandel,et al.  Proceedings of the National Academy of Sciences of the United States of America. Annual subject and author indexes. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[18]  HighWire Press,et al.  American journal of physiology. Cell physiology , 1977 .

[19]  Z. N. Demou.  Gene Expression Profiles in 3D Tumor Analogs Indicate Compressive Strain Differentially Enhances Metastatic Potential , 2010, Annals of Biomedical Engineering.

[20]  D. Drasdo,et al.  A single-cell-based model of tumor growth in vitro: monolayers and spheroids , 2005, Physical biology.

[21]  Frank Jülicher,et al.  Fluidization of tissues by cell division and apoptosis , 2010, Proceedings of the National Academy of Sciences.

[22]  Paolo A. Netti,et al.  Solid stress inhibits the growth of multicellular tumor spheroids , 1997, Nature Biotechnology.

[23]  W. Zhong,et al.  Using hyperosmolar stress to measure biologic and stress-activated protein kinase responses in preimplantation embryos. , 2007, Molecular human reproduction.

[24]  E Schöll,et al.  Comparing the growth kinetics of cell populations in two and three dimensions. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[25]  Jacques Prost,et al.  Dissipative particle dynamics simulations for biological tissues: rheology and competition , 2011, Physical biology.

[26]  R. Jain,et al.  Solid stress generated by spheroid growth estimated using a linear poroelasticity model. , 2003, Microvascular research.

[27]  R. Edwards,et al.  Molecular Human Reproduction , 1995 .

[28]  Steve Pawlizak,et al.  Are biomechanical changes necessary for tumor progression , 2010 .