scholarly journals Mathematical modeling of metastasis, a feasible way to detect the weakness

2020 ◽  
Author(s):  
A. Guerra ◽  
E. Silva ◽  
R. Mansilla ◽  
J. M. Nieto-Villar
Keyword(s):  
Mathematical Modeling ◽  
Immune System ◽  
Stability Analysis ◽  
Causes Of Death ◽  
Jacobian Matrix ◽  
Epithelial Mesenchymal Transition ◽  
Disseminated Tumor Cells ◽  
Mesenchymal Transition ◽  
Effective Strategies ◽  
Matrix Stability

AbstractAimCancer is one of the main causes of death worldwide. 90% of deaths caused by this disease occur due to metastasis. Two models are proposed that rescue fundamental aspects of metastasis, such as EMT (epithelial-mesenchymal transition), extravasation and colonization.MethodsTo evaluate the complexity, the Lyapunov exponents, the eigenvalues of the Jacobian matrix (stability analysis) and the Kaplan York dimension were calculated.ResultsIt was evidenced that the weakness of the metastasis lies in these stages, which indicates that they constitute potential targets in the search for an effective treatment.ConclusionThe results suggest that strengthening the immune system during EMT as well as its specialization in the detection of DTCs (disseminated tumor cells) can be effective strategies in the treatment of metastasis.

scholarly journals THE ROLE AND MECHANISMS OF EPITHELIAL-MESENCHYMAL TRANSITION IN THE PROGRESSION OF MELANOMA

2020 ◽  
Vol 19 (4) ◽  
pp. 8-17
Author(s):  
S. V. Chulkova ◽  
D. A. Ryabchikov ◽  
I. A. Dudina ◽  
I. V. Savchenko ◽  
A. V. Egorova ◽  
...  
Keyword(s):  
Causes Of Death ◽  
Epithelial Mesenchymal Transition ◽  
Deep Understanding ◽  
Metastatic Potential ◽  
Melanoma Cells ◽  
Modern Medicine ◽  
Mesenchymal Transition ◽  
Melanoma Progression ◽  
Leading Role ◽  
Developing Area

Despite the achievements of modern medicine in the diagnosis and treatment of oncological diseases, skin melanoma remains one of the leading causes of death worldwide: every third case of melanoma ends in death. As you know, one of the main causes of death is the high incidence of melanoma progression. It is important to note that the mechanisms of melanoma progression are diverse and the rapidly developing area of drug therapy for tumors requires a deep understanding of their characteristics. This is primarily due to the fact that these processes lead to the formation of special, minor tumor clones with stem properties. They are highly resistant to therapy. The latter is the mainobstacle to effective treatment of melanoma patients. The epithelial-mesenchymal transition (EMT) plays a leading role in the acquisition of metastatic potential by melanoma cells. An important distinguishing feature of EMT is a change in the level of expression of transmembrane glycoproteins involved in cell adhesion. With EMT, both a decrease in the level of E-cadherin and an increase in the expression of N-cadherin are observed. Such a switch in different classes of adhesion molecules leads to the fact that melanoma cells lose contact with neighboring keratinocytes and begin to interact with fibroblasts and endothelial cells. The key regulator in EMT induction in melanoma is the Notch1 signaling pathway, which accelerates N-cadherin expression when activated. In addition, EMT also regulates many other pathways – RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, Wnt/β-catenin, the dysregulation of which is associated with the development of drug resistance in melanoma. The analysis was carried out in the article of modern literature data on the importance of EMT in carcinogenesis and prognosis of melanoma. The modern mechanisms of EMT, currently known prognostic factors, as well as potential therapeutic targets that affect EMT and, accordingly, inhibit the process of metastasis, are described in detail.

scholarly journals Involvement of immune system and Epithelial–Mesenchymal-Transition in increased invasiveness of clustered circulatory tumor cells in breast cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Samane Khoshbakht ◽  
Sadegh Azimzadeh Jamalkandi ◽  
Ali Masudi-Nejad
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Tumor Cells ◽  
Distant Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Rank Test ◽  
Support Vector ◽  
Mesenchymal Transition ◽  
Menstrual Cycles

Abstract Background Circulating tumor cells (CTCs) are the critical initiators of distant metastasis formation. In which, the reciprocal interplay among different metastatic pathways and their metastasis driver genes which promote survival of CTCs is not well introduced using network approaches. Methods Here, to investigate the unknown pathways of single/cluster CTCs, the co-expression network was reconstructed, using WGCNA (Weighted Correlation Network Analysis) method. Having used the hierarchical clustering, we detected the Immune-response and EMT subnetworks. The metastatic potential of genes was assessed and validated through the support vector machine (SVM), neural network, and decision tree methods on two external datasets. To identify the active signaling pathways in CTCs, we reconstructed a casual network. The Log-Rank test and Kaplan–Meier curve were applied to detect prognostic gene signatures for distant metastasis-free survival (DMFS). Finally, a predictive model was developed for metastasis risk of patients using VIF-stepwise feature selection. Results Our results showed the crosstalk among EMT, the immune system, menstrual cycles, and the stemness pathway in CTCs. In which, fluctuation of menstrual cycles is a new detected pathway in breast cancer CTCs. The reciprocal association between immune responses and EMT was identified in CTCs. The SVM model indicated a high metastatic potential of EMT subnetwork (accuracy, sensitivity, and specificity scores were 87%). The DMFS model was identified to predict patients’ metastasis risks. (c-index = 0.7). Finally, novel metastatic biomarkers of KRT18 and KRT19 were detected in breast cancer CTCs. Conclusions In conclusion, the reciprocal interplay among critical unknown pathways in CTCs manifests both their survival in blood and metastatic potentials. Such findings may help to develop more precise predictive metastatic-risk models or detect pivotal metastatic biomarkers.

scholarly journals Cooperative and Escaping Mechanisms between Circulating Tumor Cells and Blood Constituents

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1382 ◽  
Author(s):  
Garrido-Navas ◽  
de Miguel-Perez ◽  
Exposito-Hernandez ◽  
Bayarri ◽  
Amezcua ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Blood Constituents ◽  
Commensal Microbiota ◽  
Underlying Mechanisms

Metastasis is the leading cause of cancer-related deaths and despite measurable progress in the field, underlying mechanisms are still not fully understood. Circulating tumor cells (CTCs) disseminate within the bloodstream, where most of them die due to the attack of the immune system. On the other hand, recent evidence shows active interactions between CTCs and platelets, myeloid cells, macrophages, neutrophils, and other hematopoietic cells that secrete immunosuppressive cytokines, which aid CTCs to evade the immune system and enable metastasis. Platelets, for instance, regulate inflammation, recruit neutrophils, and cause fibrin clots, which may protect CTCs from the attack of Natural Killer cells or macrophages and facilitate extravasation. Recently, a correlation between the commensal microbiota and the inflammatory/immune tone of the organism has been stablished. Thus, the microbiota may affect the development of cancer-promoting conditions. Furthermore, CTCs may suffer phenotypic changes, as those caused by the epithelial–mesenchymal transition, that also contribute to the immune escape and resistance to immunotherapy. In this review, we discuss the findings regarding the collaborative biological events among CTCs, immune cells, and microbiome associated to immune escape and metastatic progression.

scholarly journals The Vicious Cross-Talk between Tumor Cells with an EMT Phenotype and Cells of the Immune System

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 460 ◽  
Author(s):  
Elisabetta Romeo ◽  
Carmelo Antonio Caserta ◽  
Cristiano Rumio ◽  
Fabrizio Marcucci
Keyword(s):  
Immune System ◽  
Tumor Cells ◽  
Cross Talk ◽  
Immune Cells ◽  
Epithelial Mesenchymal Transition ◽  
Large Body ◽  
Adaptive Immune System ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Immune Exclusion

Carcinoma cells that undergo an epithelial-mesenchymal transition (EMT) and display a predominantly mesenchymal phenotype (hereafter EMT tumor cells) are associated with immune exclusion and immune deviation in the tumor microenvironment (TME). A large body of evidence has shown that EMT tumor cells and immune cells can reciprocally influence each other, with EMT cells promoting immune exclusion and deviation and immune cells promoting, under certain circumstances, the induction of EMT in tumor cells. This cross-talk between EMT tumor cells and immune cells can occur both between EMT tumor cells and cells of either the native or adaptive immune system. In this article, we review this evidence and the functional consequences of it. We also discuss some recent evidence showing that tumor cells and cells of the immune system respond to similar stimuli, activate the expression of partially overlapping gene sets, and acquire, at least in part, identical functionalities such as migration and invasion. The possible significance of these symmetrical changes in the cross-talk between EMT tumor cells and immune cells is addressed. Eventually, we also discuss possible therapeutic opportunities that may derive from disrupting this cross-talk.

scholarly journals Unique cellular protrusions mediate breast cancer cell migration by tethering to osteogenic cells

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Aaron M. Muscarella ◽  
Wei Dai ◽  
Patrick G. Mitchell ◽  
Weijie Zhang ◽  
Hai Wang ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Metastatic Cancer ◽  
Disseminated Tumor Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Osteogenic Cells ◽  
Cellular Protrusion

Abstract Migration and invasion are key properties of metastatic cancer cells. These properties can be acquired through intrinsic reprogramming processes such as epithelial-mesenchymal transition. In this study, we discovered an alternative “migration-by-tethering” mechanism through which cancer cells gain the momentum to migrate by adhering to mesenchymal stem cells or osteoblasts. This tethering is mediated by both heterotypic adherens junctions and gap junctions, and leads to a unique cellular protrusion supported by cofilin-coated actin filaments. Inhibition of gap junctions or depletion of cofilin reduces migration-by-tethering. We observed evidence of these protrusions in bone segments harboring experimental and spontaneous bone metastasis in animal models. These data exemplify how cancer cells may acquire migratory ability without intrinsic reprogramming. Furthermore, given the important roles of osteogenic cells in early-stage bone colonization, our observations raise the possibility that migration-by-tethering may drive the relocation of disseminated tumor cells between different niches in the bone microenvironment.

Modeling continuum of epithelial mesenchymal transition plasticity

2016 ◽  
Vol 8 (2) ◽  
pp. 167-176 ◽  
Author(s):  
Mousumi Mandal ◽  
Biswajoy Ghosh ◽  
Anji Anura ◽  
Pabitra Mitra ◽  
Tanmaya Pathak ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Cell Population ◽  
Epithelial Mesenchymal Transition ◽  
Hacat Cell ◽  
Mesenchymal Transition

Mathematical modeling of plasticity expressed in EMT undergoing HaCaT cell population endorsed with molecular expressions and phenotype morphometry.

scholarly journals Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingjie Liu ◽  
Peiyuan Zhang ◽  
Qiuyao Wu ◽  
Houqin Fang ◽  
Yuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Disseminated Tumor Cells ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Tumor Dissemination ◽  
Long Non Coding Rna

AbstractDisseminated tumor cells often fall into a long term of dormant stage, characterized by decreased proliferation but sustained survival, in distant organs before awakening for metastatic growth. However, the regulatory mechanism of metastatic dormancy and awakening is largely unknown. Here, we show that the epithelial-like and mesenchymal-like subpopulations of breast cancer stem-like cells (BCSCs) demonstrate different levels of dormancy and tumorigenicity in lungs. The long non-coding RNA (lncRNA) NR2F1-AS1 (NAS1) is up-regulated in the dormant mesenchymal-like BCSCs, and functionally promotes tumor dissemination but reduces proliferation in lungs. Mechanistically, NAS1 binds to NR2F1 mRNA and recruits the RNA-binding protein PTBP1 to promote internal ribosome entry site (IRES)-mediated NR2F1 translation, thus leading to suppression of ΔNp63 transcription by NR2F1. Furthermore, ΔNp63 downregulation results in epithelial-mesenchymal transition, reduced tumorigenicity and enhanced dormancy of cancer cells in lungs. Overall, the study links BCSC plasticity with metastatic dormancy, and reveals the lncRNA as an important regulator of both processes.

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