Modeling <i>TGF</i>-β signaling pathway in epithelial-mesenchymal transition

Laise, Pasquale; Fanelli, Duccio; Lió, Píetro; Arcangeli, Annarosa

doi:10.1063/1.3697962

Cited by 4 publications

(10 citation statements)

References 19 publications

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“…For example, we can integrate the signaling pathways into the model, as EMT or MET are regulated by the ligands or molecules outside cells to activate related signaling inside the cells. The secretion and diffusion of the ligands can be described by partial differential equations (PDEs) (61), and the dynamics of signaling cascades could be formulated by ordinary differential equations (ODEs) (64). Moreover, the cell growth can be described by increasing the size of cells over time, which is also regulated by the availability of nutrients around them.…”

Section: Mathematical Modeling Of Emtmentioning

confidence: 99%

Microenvironmental Regulation of Epithelial–Mesenchymal Transitions in Cancer

et al. 2012

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The evolution of the cancer cell into a metastatic entity is the major cause of death in cancer patients. Activation of epithelial to mesenchymal transition (EMT) endows invasive and metastatic properties upon cancer cells that favor successful colonization of distal target organs. The observation that in many cancers distant metastases resemble the epithelial phenotype of primary tumors has led to speculation that the disseminated tumor cells recruited to the target organs undergo mesenchymal to epithelial transition (MET). However, the MET cascade has not been recapitulated in vivo, and the cellular and molecular regulators that promote MET remain unknown. In a recent report, using a model of spontaneous breast cancer, we have shown that bone marrow (BM)-derived myeloid progenitor cells in the premetastatic lung secrete the proteoglycan versican, which induces MET of metastatic tumor cells and accelerates metastases. This review summarizes recent progress in MET research and outlines a unique paracrine cross talk between the microenvironment and the cancer cells that promotes tumor outgrowth in the metastatic organ and discusses opportunities for novel antimetastatic approaches for cancer therapy.

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Section: Mathematical Modeling Of Emtmentioning

confidence: 99%

Microenvironmental Regulation of Epithelial–Mesenchymal Transitions in Cancer

et al. 2012

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“…Given the different time dynamics of the reactions at the intracellular pathways level and the cell dynamics at tissue levels, we prefer to build distinct models, coupled by time averages of the fastest dynamics. Following the model developed by Laise et al [14] , we have focused on autocriny and paracriny behaviours of the - . Next, we have considered a tissue model to describe the effects of the - on cellular populations characterized by different driver mutations.…”

Section: Resultsmentioning

confidence: 99%

“…In reality, different isoforms of - and of its receptor exist. In [14] , the authors simplify the model setting by considering just one receptor type, which can operate in its active (bound to - ) or inactive configuration. The activated receptor is able to phosphorylate the -Smad proteins ( ) in the cytoplasm, resulting in the formation of a new species, the phosphorylated Smad protein, here labelled .…”

Section: Resultsmentioning

confidence: 99%

“…The - pathway is in particular reduced to a limited set of meaningful chemical reactions that are presumably implicated in the transmission of the signal from the cell surface, as triggered by - , to the cell nucleus. The analysis conducted by the authors in [14] is in particular aimed at inspecting the out-of-equilibrium dynamics of the system, as driven by the externally imposed - . The model proposed by Laise et al for the epithelial-mesenchymal transition predicts the concentration of mRNA associated to gene , properly describes the results of the in-vitro experiments set up by [16] and reproduces the right unperturbed steady state characterized by specific concentrations of cytoplasmatic Smad proteins and unbound receptors , which have been carefully evaluated by Schmierer and collaborators.…”

Section: Resultsmentioning

confidence: 99%

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Modeling TGF-β in Early Stages of Cancer Tissue Dynamics

Ascolani

Lió

2014

PLoS ONE

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Recent works have highlighted a double role for the Transforming Growth Factor (-): it inhibits cancer in healthy cells and potentiates tumor progression during late stage of tumorigenicity, respectively; therefore it has been termed the “Jekyll and Hyde” of cancer or, alternatively, an “excellent servant but a bad master”. It remains unclear how this molecule could have the two opposite behaviours. In this work, we propose a - multi scale mathematical model at molecular, cellular and tissue scales. The multi scalar behaviours of the - are described by three coupled models built up together which can approximatively be related to distinct microscopic, mesoscopic, and macroscopic scales, respectively. We first model the dynamics of - at the single-cell level by taking into account the intracellular and extracellular balance and the autocrine and paracrine behaviour of -. Then we use the average estimates of the - from the first model to understand its dynamics in a model of duct breast tissue. Although the cellular model and the tissue model describe phenomena at different time scales, their cumulative dynamics explain the changes in the role of - in the progression from healthy to pre-tumoral to cancer. We estimate various parameters by using available gene expression datasets. Despite the fact that our model does not describe an explicit tissue geometry, it provides quantitative inference on the stage and progression of breast cancer tissue invasion that could be compared with epidemiological data in literature. Finally in the last model, we investigated the invasion of breast cancer cells in the bone niches and the subsequent disregulation of bone remodeling processes. The bone model provides an effective description of the bone dynamics in healthy and early stages cancer conditions and offers an evolutionary ecological perspective of the dynamics of the competition between cancer and healthy cells.

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“…Our own paper with Chris Cleveland 8 on "Physics of cancer propagation: a game theory perspective" tries to look at cancer invasion from a game theoretic perspective as opposed to a strictly physical one. Our paper brings up the subject of information transfer in cancer, and this is explored by Laise et al 9 ("Modeling TGF-β signaling pathway in epithelial-mesenchymal transition").…”

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confidence: 99%