Elastic Free Energy Drives the Shape of Prevascular Solid Tumors

Mills, Kristen; Kemkemer, Ralf; Rudraraju, Shiva; Garikipati, Krishna

doi:10.1371/journal.pone.0103245

Cited by 32 publications

(28 citation statements)

References 43 publications

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“…Increasing the Von Mises stress caused by both BPH and PCa in the prostatic tissue between the tumor and the prostate A1 B1 A2 B2 external boundary would also contribute to prevent the tumor from escaping the prostate. The arrangement of tumor growth and geometry to its local mechanical environment was also previously observed and measured in in vitro experiments (25,49). These studies along with our results highlight the major role of mechanical modulation of the shape and size of growing solid tumors, which are key pieces of information for clinical staging.…”

Section: Discussionsupporting

confidence: 83%

Computer simulations suggest that prostate enlargement due to benign prostatic hyperplasia mechanically impedes prostate cancer growth

Lorenzo

Hughes

Dominguez-Frojan

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

105

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Prostate cancer and benign prostatic hyperplasia are common genitourinary diseases in aging men. Both pathologies may coexist and share numerous similarities, which have suggested several connections or some interplay between them. However, solid evidence confirming their existence is lacking. Recent studies on extensive series of prostatectomy specimens have shown that tumors originating in larger prostates present favorable pathological features. Hence, large prostates may exert a protective effect against prostate cancer. In this work, we propose a mechanical explanation for this phenomenon. The mechanical stress fields that originate as tumors enlarge have been shown to slow down their dynamics. Benign prostatic hyperplasia contributes to these mechanical stress fields, hence further restraining prostate cancer growth. We derived a tissuescale, patient-specific mechanically coupled mathematical model to qualitatively investigate the mechanical interaction of prostate cancer and benign prostatic hyperplasia. This model was calibrated by studying the deformation caused by each disease independently. Our simulations show that a history of benign prostatic hyperplasia creates mechanical stress fields in the prostate that impede prostatic tumor growth and limit its invasiveness. The technology presented herein may assist physicians in the clinical management of benign prostate hyperplasia and prostate cancer by predicting pathological outcomes on a tissue-scale, patient-specific basis.prostate cancer | benign prostatic hyperplasia | mathematical oncology | patient-specific | isogeometric analysis

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Section: Discussionsupporting

confidence: 83%

Computer simulations suggest that prostate enlargement due to benign prostatic hyperplasia mechanically impedes prostate cancer growth

Lorenzo

Hughes

Dominguez-Frojan

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

105

View full text Add to dashboard Cite

show abstract

“…1 is defined in a more sophisticated fashion. Another aspect of interest is the study of mechanical stress on tumor growth, which has been studied experimentally (66,67) and computationally (68). This could be particularly important in PCa, because the prostate is subjected to significant mechanical confinement.…”

Section: Discussionmentioning

confidence: 99%

Tissue-scale, personalized modeling and simulation of prostate cancer growth

Lorenzo

Scott

Tew

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed “predictive medicine.” Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion−reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice.

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“…The literature on computational treatments of biological growth also has, in our eyes, suffered a limitation: problems addressable by the model of inhomogeneous, volume growth, i.e., morphoelasticity, have formed the mainstay of this body of work. Effective as this treatment has been in explaining tumor growth [40][41][42], aspects of cardiovascular systems, and the folding of soft, layered structures during morphogenesis [43], it cannot be elegantly extended to accretive, surface growth. For such problems, the morphoelastic treatment is restricted to representing advancing fronts by a thickening surface layer.…”

Section: Discussionmentioning

confidence: 99%

A computational framework for the morpho-elastic development of molluskan shells by surface and volume growth

et al. 2019

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Mollusk shells are an ideal model system for understanding the morpho-elastic basis of morphological evolution of invertebrates’ exoskeletons. During the formation of the shell, the mantle tissue secretes proteins and minerals that calcify to form a new incremental layer of the exoskeleton. Most of the existing literature on the morphology of mollusks is descriptive. The mathematical understanding of the underlying coupling between pre-existing shell morphology, de novo surface deposition and morpho-elastic volume growth is at a nascent stage, primarily limited to reduced geometric representations. Here, we propose a general, three-dimensional computational framework coupling pre-existing morphology, incremental surface growth by accretion, and morpho-elastic volume growth. We exercise this framework by applying it to explain the stepwise morphogenesis of seashells during growth: new material surfaces are laid down by accretive growth on the mantle whose form is determined by its morpho-elastic growth. Calcification of the newest surfaces extends the shell as well as creates a new scaffold that constrains the next growth step. We study the effects of surface and volumetric growth rates, and of previously deposited shell geometries on the resulting modes of mantle deformation, and therefore of the developing shell’s morphology. Connections are made to a range of complex shells ornamentations.

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Elastic Free Energy Drives the Shape of Prevascular Solid Tumors

Cited by 32 publications

References 43 publications

Computer simulations suggest that prostate enlargement due to benign prostatic hyperplasia mechanically impedes prostate cancer growth

Computer simulations suggest that prostate enlargement due to benign prostatic hyperplasia mechanically impedes prostate cancer growth

Tissue-scale, personalized modeling and simulation of prostate cancer growth

A computational framework for the morpho-elastic development of molluskan shells by surface and volume growth

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