Evolution and morphology of microenvironment-enhanced malignancy of three-dimensional invasive solid tumors

Yang Jiao, Salvatore Torquato

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The emergence of invasive and metastatic behavior in malignant tumors can often lead to fatal outcomes for patients. The collective malignant tumor behavior resulting from the complex tumor-host interactions and the interactions between the tumor cells is currently poorly understood. In this paper, we employ a cellular automaton (CA) model to investigate microenvironment-enhanced malignant behaviors and morphologies of in vitro avascular invasive solid tumors in three dimensions. Our CA model incorporates a variety of microscopic-scale tumor-host interactions, including the degradation of the extracellular matrix by the malignant cells, nutrient-driven cell migration, pressure buildup due to the deformation of the microenvironment by the growing tumor, and its effect on the local tumor-host interface stability. Moreover, the effects of cell-cell adhesion on tumor growth are explicitly taken into account. Specifically, we find that while strong cell-cell adhesion can suppress the invasive behavior of the tumors growing in soft microenvironments, cancer malignancy can be significantly enhanced by harsh microenvironmental conditions, such as exposure to high pressure levels. We infer from the simulation results a qualitative phase diagram that characterizes the expected malignant behavior of invasive solid tumors in terms of two competing malignancy effects: the rigidity of the microenvironment and cell-cell adhesion. This diagram exhibits phase transitions between noninvasive and invasive behaviors. We also discuss the implications of our results for the diagnosis, prognosis, and treatment of malignant tumors.

Original languageEnglish (US)
Article number052707
JournalPhysical Review E - Statistical, Nonlinear, and Soft Matter Physics
Volume87
Issue number5
DOIs
StatePublished - May 13 2013
Externally publishedYes

Fingerprint

Tumor
tumors
Three-dimensional
Neoplasms
Cell Adhesion
cells
Cell
Cellular Automaton Model
adhesion
Tumor Microenvironment
cellular automata
Interaction
phase diagrams
interface stability
Cell Migration
Tumor Growth
Prognosis
Cellular Microenvironment
Pressure
prognosis

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Statistical and Nonlinear Physics
  • Statistics and Probability
  • Medicine(all)

Cite this

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title = "Evolution and morphology of microenvironment-enhanced malignancy of three-dimensional invasive solid tumors",
abstract = "The emergence of invasive and metastatic behavior in malignant tumors can often lead to fatal outcomes for patients. The collective malignant tumor behavior resulting from the complex tumor-host interactions and the interactions between the tumor cells is currently poorly understood. In this paper, we employ a cellular automaton (CA) model to investigate microenvironment-enhanced malignant behaviors and morphologies of in vitro avascular invasive solid tumors in three dimensions. Our CA model incorporates a variety of microscopic-scale tumor-host interactions, including the degradation of the extracellular matrix by the malignant cells, nutrient-driven cell migration, pressure buildup due to the deformation of the microenvironment by the growing tumor, and its effect on the local tumor-host interface stability. Moreover, the effects of cell-cell adhesion on tumor growth are explicitly taken into account. Specifically, we find that while strong cell-cell adhesion can suppress the invasive behavior of the tumors growing in soft microenvironments, cancer malignancy can be significantly enhanced by harsh microenvironmental conditions, such as exposure to high pressure levels. We infer from the simulation results a qualitative phase diagram that characterizes the expected malignant behavior of invasive solid tumors in terms of two competing malignancy effects: the rigidity of the microenvironment and cell-cell adhesion. This diagram exhibits phase transitions between noninvasive and invasive behaviors. We also discuss the implications of our results for the diagnosis, prognosis, and treatment of malignant tumors.",
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