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Role of constitutive behavior and tumor-host mechanical interactions in the state of stress and growth of solid tumors.

Voutouri C, Mpekris F, Papageorgis P, Odysseos AD, Stylianopoulos T - PLoS ONE (2014)

Bottom Line: To this end, we performed unconfined compression experiments in two tumor types and found that the experimental stress-strain response is better fitted to an exponential constitutive equation compared to the widely used neo-Hookean and Blatz-Ko models.Interestingly, we found that the evolution of stress and the growth rate of the tumor are independent from the selection of the constitutive equation, but depend strongly on the mechanical interactions with the surrounding host tissue.Our results suggest that the direct effect of solid stress on tumor growth involves not only the inhibitory effect of stress on cancer cell proliferation and the induction of apoptosis, but also the resistance of the surrounding tissue to tumor expansion.

View Article: PubMed Central - PubMed

Affiliation: Cancer Biophysics laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.

ABSTRACT
Mechanical forces play a crucial role in tumor patho-physiology. Compression of cancer cells inhibits their proliferation rate, induces apoptosis and enhances their invasive and metastatic potential. Additionally, compression of intratumor blood vessels reduces the supply of oxygen, nutrients and drugs, affecting tumor progression and treatment. Despite the great importance of the mechanical microenvironment to the pathology of cancer, there are limited studies for the constitutive modeling and the mechanical properties of tumors and on how these parameters affect tumor growth. Also, the contribution of the host tissue to the growth and state of stress of the tumor remains unclear. To this end, we performed unconfined compression experiments in two tumor types and found that the experimental stress-strain response is better fitted to an exponential constitutive equation compared to the widely used neo-Hookean and Blatz-Ko models. Subsequently, we incorporated the constitutive equations along with the corresponding values of the mechanical properties - calculated by the fit - to a biomechanical model of tumor growth. Interestingly, we found that the evolution of stress and the growth rate of the tumor are independent from the selection of the constitutive equation, but depend strongly on the mechanical interactions with the surrounding host tissue. Particularly, model predictions - in agreement with experimental studies - suggest that the stiffness of solid tumors should exceed a critical value compared with that of the surrounding tissue in order to be able to displace the tissue and grow in size. With the use of the model, we estimated this critical value to be on the order of 1.5. Our results suggest that the direct effect of solid stress on tumor growth involves not only the inhibitory effect of stress on cancer cell proliferation and the induction of apoptosis, but also the resistance of the surrounding tissue to tumor expansion.

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Stress-strain response of tumors.Experimentally measured elastic stress-strain response of MCF10CA1a and SW620 tumors in unconfined compression. Data show individual tumor behavior.
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pone-0104717-g002: Stress-strain response of tumors.Experimentally measured elastic stress-strain response of MCF10CA1a and SW620 tumors in unconfined compression. Data show individual tumor behavior.

Mentions: The experimental results of the unconfined compression experiments for the individual tumors and for the two tumor types are shown in Figure 2. The equilibrium stress-strain response is highly nonlinear in most of the specimens even at the low range of strain employed in the study. The data are typical of soft biological tissues, consisting of a toe region at lower strains and a linear region at higher strains. The elastic modulus was measured from the slope of the linear part of the curves and found to be 288.3±45.5 kPa for the MCF10CA1a tumors and 186.1±25.9 kPa for the SW620 tumors. The difference between the two groups was not statistically significant (p = 0.065). The values of tan(δ) was 0.108±0.009 and 0.098±0.011 for the MCF10CA1a and SW620, respectively (Table 1). The results were not statistically different (p = 0.106).


Role of constitutive behavior and tumor-host mechanical interactions in the state of stress and growth of solid tumors.

Voutouri C, Mpekris F, Papageorgis P, Odysseos AD, Stylianopoulos T - PLoS ONE (2014)

Stress-strain response of tumors.Experimentally measured elastic stress-strain response of MCF10CA1a and SW620 tumors in unconfined compression. Data show individual tumor behavior.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128744&req=5

pone-0104717-g002: Stress-strain response of tumors.Experimentally measured elastic stress-strain response of MCF10CA1a and SW620 tumors in unconfined compression. Data show individual tumor behavior.
Mentions: The experimental results of the unconfined compression experiments for the individual tumors and for the two tumor types are shown in Figure 2. The equilibrium stress-strain response is highly nonlinear in most of the specimens even at the low range of strain employed in the study. The data are typical of soft biological tissues, consisting of a toe region at lower strains and a linear region at higher strains. The elastic modulus was measured from the slope of the linear part of the curves and found to be 288.3±45.5 kPa for the MCF10CA1a tumors and 186.1±25.9 kPa for the SW620 tumors. The difference between the two groups was not statistically significant (p = 0.065). The values of tan(δ) was 0.108±0.009 and 0.098±0.011 for the MCF10CA1a and SW620, respectively (Table 1). The results were not statistically different (p = 0.106).

Bottom Line: To this end, we performed unconfined compression experiments in two tumor types and found that the experimental stress-strain response is better fitted to an exponential constitutive equation compared to the widely used neo-Hookean and Blatz-Ko models.Interestingly, we found that the evolution of stress and the growth rate of the tumor are independent from the selection of the constitutive equation, but depend strongly on the mechanical interactions with the surrounding host tissue.Our results suggest that the direct effect of solid stress on tumor growth involves not only the inhibitory effect of stress on cancer cell proliferation and the induction of apoptosis, but also the resistance of the surrounding tissue to tumor expansion.

View Article: PubMed Central - PubMed

Affiliation: Cancer Biophysics laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.

ABSTRACT
Mechanical forces play a crucial role in tumor patho-physiology. Compression of cancer cells inhibits their proliferation rate, induces apoptosis and enhances their invasive and metastatic potential. Additionally, compression of intratumor blood vessels reduces the supply of oxygen, nutrients and drugs, affecting tumor progression and treatment. Despite the great importance of the mechanical microenvironment to the pathology of cancer, there are limited studies for the constitutive modeling and the mechanical properties of tumors and on how these parameters affect tumor growth. Also, the contribution of the host tissue to the growth and state of stress of the tumor remains unclear. To this end, we performed unconfined compression experiments in two tumor types and found that the experimental stress-strain response is better fitted to an exponential constitutive equation compared to the widely used neo-Hookean and Blatz-Ko models. Subsequently, we incorporated the constitutive equations along with the corresponding values of the mechanical properties - calculated by the fit - to a biomechanical model of tumor growth. Interestingly, we found that the evolution of stress and the growth rate of the tumor are independent from the selection of the constitutive equation, but depend strongly on the mechanical interactions with the surrounding host tissue. Particularly, model predictions - in agreement with experimental studies - suggest that the stiffness of solid tumors should exceed a critical value compared with that of the surrounding tissue in order to be able to displace the tissue and grow in size. With the use of the model, we estimated this critical value to be on the order of 1.5. Our results suggest that the direct effect of solid stress on tumor growth involves not only the inhibitory effect of stress on cancer cell proliferation and the induction of apoptosis, but also the resistance of the surrounding tissue to tumor expansion.

Show MeSH
Related in: MedlinePlus