The role of the microenvironment in tumor invasion

Kim, Yangjin; Lim, Sookkyung

doi:10.1137/1.9781611973303.10

“…Blocking TGF-β and its receptors was suggested to a therapeutic approach due to their ability to inhibit tumor growth [32,139] and critical cell invasion [31,140,141], decrease tumourigenic potential [139,142], and reduce metastatic dissemination [143] through various different pathways including the SMADs family [29,144]. We showed that inhibition of TGF-β can effectively decrease migration potential of tumor cell cells through the transfilter by reducing the critical interaction between neutrophils and tumor cells ( Fig 10, Fig 15).…”

Section: The Role Of Mmps In Regulation Of Cancer Cell Invasion and Mmentioning

confidence: 87%

“…In particular, neutrophil-to-lymphocyte ratio (NLR) in blood was shown to be an important prognostic factor for cancer progression [134][135][136][137] including lung cancers [9,138]. Blocking TGF-β and its receptors was shown to inhibit tumor growth [32,139] and critical cell invasion [31,140,141], decrease tumourigenic potential [139,142], and reduce metastatic incidence [143] through many different pathways [29,144]. In order to investigate the effect of TGF-β suppression on tumor cell invasion.…”

Section: Application Of the Modelmentioning

confidence: 99%

Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural Insights from a Computational Model

Lee

¹

,

Lee

²

,

Lawler

³

et al. 2020

Preprint

Self Cite

0

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Lung cancer is one of the leading causes of cancer-related deaths worldwide and is characterized by hijacking immune system for active growth and aggressive metastasis. Neutrophils, which in their original form should establish immune activities to the tumor as a first line of defense, are undermined by tumor cells to promote tumor invasion in several ways. In this study, we investigate the mutual interactions between the tumor cells and the neutrophils that facilitate tumor invasion by developing a mathematical model that involves taxis-reaction-diffusion equations for the critical components in the interaction. These include the densities of tumor and neutrophils, and the concentrations of signaling molecules and structure such as neutrophil extracellular traps (NETs). We apply the mathematical model to a Boyden invasion assay used in the experiments to demonstrate that the tumor-associated neutrophils can enhance tumor cell invasion by secreting the neutrophil elastase. We show that the model can both reproduce the major experimental observation on NET-mediated cancer invasion and make several important predictions to guide future experiments with the goal of the development of new anti-tumor strategies. Moreover, using this model, we investigate the fundamental mechanism of NET-mediated invasion of cancer cells and the impact of internal and external heterogeneity on the migration patterning of tumour cells and their response to different treatment schedules.

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Modeling the Role of TGF-β in Regulation of the Th17 Phenotype in the LPS-Driven Immune System

Lee

¹

,

Hwang

²

,

Kim

³

2014

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Airway exposure levels of lipopolysaccharide (LPS) are known to determine type I versus type II helper T cell induced experimental asthma. While low doses of LPS derive Th2 inflammatory responses, high (and/or intermediate) LPS levels induce Th1- or Th17-dominant responses. The present paper develops a mathematical model of the phenotypic switches among three Th phenotypes (Th1, Th2, and Th17) in response to various LPS levels. In the present work, we simplify the complex network of the interactions between cells and regulatory molecules. The model describes the nonlinear cross-talks between the IL-4/Th2 activities and a key regulatory molecule, transforming growth factor β (TGF-β), in response to high, intermediate, and low levels of LPS. The model characterizes development of three phenotypes (Th1, Th2, and Th17) and predicts the onset of a new phenotype, Th17, under the tight control of TGF-β. Analysis of the model illustrates the mono-, bi-, and oneway-switches in the key regulatory parameter sets in the absence or presence of time delays. The model also predicts coexistence of those phenotypes and Th1- or Th2-dominant immune responses in a spatial domain under various biochemical and bio-mechanical conditions in the microenvironment.

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Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural insights from a computational model

Lee¹,

Lee²,

Lawler³

et al. 2021

Self Cite

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Lung cancer is one of the leading causes of cancer-related deaths worldwide and is characterized by hijacking immune system for active growth and aggressive metastasis. Neutrophils, which in their original form should establish immune activities to the tumor as a first line of defense, are undermined by tumor cells to promote tumor invasion in several ways. In this study, we investigate the mutual interactions between the tumor cells and the neutrophils that facilitate tumor invasion by developing a mathematical model that involves taxis-reaction-diffusion equations for the critical components in the interaction. These include the densities of tumor and neutrophils, and the concentrations of signaling molecules and structure such as neutrophil extracellular traps (NETs). We apply the mathematical model to a Boyden invasion assay used in the experiments to demonstrate that the tumor-associated neutrophils can enhance tumor cell invasion by secreting the neutrophil elastase. We show that the model can both reproduce the major experimental observation on NET-mediated cancer invasion and make several important predictions to guide future experiments with the goal of the development of new anti-tumor strategies. Moreover, using this model, we investigate the fundamental mechanism of NET-mediated invasion of cancer cells and the impact of internal and external heterogeneity on the migration patterning of tumour cells and their response to different treatment schedules.

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The role of the microenvironment in tumor invasion

Cited by 4 publications

References 43 publications

Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural Insights from a Computational Model

Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural Insights from a Computational Model

Modeling the Role of TGF-β in Regulation of the Th17 Phenotype in the LPS-Driven Immune System

Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural insights from a computational model

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