Abstract
Complex tumor-host interactions can significantly affect the growth dynamics and morphologies of progressing neoplasms. The growth of a confined solid tumor induces mechanical pressure and deformation of the surrounding microenvironment, which in turn influences tumor growth. In this paper, we generalize a recently developed cellular automaton model for invasive tumor growth in heterogeneous microenvironments [Y. Jiao and S. Torquato, PLoS Comput. Biol.7, e1002314 (2011)] by incorporating the effects of pressure. Specifically, we explicitly model the pressure exerted on the growing tumor due to the deformation of the microenvironment and its effect on the local tumor-host interface instability. Both noninvasive-proliferative growth and invasive growth with individual cells that detach themselves from the primary tumor and migrate into the surrounding microenvironment are investigated. We find that while noninvasive tumors growing in "soft" homogeneous microenvironments develop almost isotropic shapes, both high pressure and host heterogeneity can strongly enhance malignant behavior, leading to finger-like protrusions of the tumor surface. Moreover, we show that individual invasive cells of an invasive tumor degrade the local extracellular matrix at the tumor-host interface, which diminishes the fingering growth of the primary tumor. The implications of our results for cancer diagnosis, prognosis and therapy are discussed.
Highlights
IntroductionTumor malignancy arises from many complex interactions occurring between the tumor and its host microenvironment.[1,2] There is increasing evidence that the host microenvironment can significantly affect neoplasm progression.[3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20] The growth of a confined solid tumor produces mechanical pressure, leading to deformation of the surrounding microenvironment, which generally affects the growth dynamics of the tumor.[21] Such pressure can result in clinical complications, especially in a confined region of space such as the brain[22] and deform or even collapse the intra-tumoral blood and lymphatic vessels.[23] It has been hypothesized that pressure may influence tumor physiology, growth rate and morphology.[21] understanding effects of pressure on tumor growth is important for both fundamental cancer research and clinical practice.[21]
We have explicitly taken into account the deformation of the extracellular matrix surrounding the tumor, which in turn imposes pressure on the neoplasm
We showed that by varying the extracellular matrix (ECM) rigidity, one can obtain a variety of tumor morphologies ranging from spherical shapes to fingering patterns, which are quantitatively characterized by the specific surface
Summary
Tumor malignancy arises from many complex interactions occurring between the tumor and its host microenvironment.[1,2] There is increasing evidence that the host microenvironment can significantly affect neoplasm progression.[3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20] The growth of a confined solid tumor produces mechanical pressure, leading to deformation of the surrounding microenvironment, which generally affects the growth dynamics of the tumor.[21] Such pressure can result in clinical complications, especially in a confined region of space such as the brain[22] and deform or even collapse the intra-tumoral blood and lymphatic vessels.[23] It has been hypothesized that pressure may influence tumor physiology, growth rate and morphology.[21] understanding effects of pressure on tumor growth is important for both fundamental cancer research and clinical practice.[21]
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