Network Inference from Cancer and Epithelial Cell Co-Culture Reveal Microenvironmental Configurations That Drives Population Dynamics DOI Open Access
Alexandre Sarmento Queiroga, Mauro César Cafundó Morais, Beatriz Stransky

et al.

Published: Nov. 2, 2023

Cellular Automata and Boolean Networks are generalizations of one another because algorithms to compute the preimage cellular automata reveal underlying network, i.e., global dynamics in terms basins attraction. Therefore, we hypothesize can local from basin attraction an inferred boolean network. Our motivation was observation that human keratinocytes melanoma stick together form clusters after eight days co-culture. This cluster formation would be attractor population dynamics, cell seeding initial condition Hence, propose a method estimate rules automata, which consist comparing density states within each state transition reaching consensus among transitions belonging aim: (1) infer network \emph{in vitro} co-culture growth curve; (2) automata; (3) implement for spatial simulations. The binarization curve shows high four days; estimated were compatible with proliferation migration agreement experimental observations. Spatial that: exhibit higher neighborhoods where is present; chance keratinocyte increases until fourth day, but probability survival increases; space freed cells maximum capacity through compensated by death. approach suggests induced increase survival, as well balance death concerning melanoma. has potential offer valuable clues about microenvironmental interactions or configurations drive dynamics.

Language: Английский

The Keratinocyte in the Picture Cutaneous Melanoma Microenvironment DOI Open Access
Ramona Marrapodi, Barbara Bellei

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 913 - 913

Published: Feb. 23, 2024

Melanoma progression is a multistep evolution from common melanocytic nevus through radial superficial growth phase, the invasive vertical phase finally leading to metastatic dissemination into distant organs. aggressiveness largely depends on propensity metastasize, which means capacity escape physiological microenvironment since tissue damage due primary melanoma lesions generally modest. Physiologically, epidermal melanocytes are attached basement membrane, and their adhesion/migration under control of surrounding keratinocytes. Thus, compartment represents first responsible for spread. This complex process involves cell-cell contact broad range secreted bioactive molecules. Invasion, or at beginning microinvasion, implies breakdown dermo-epidermal membrane followed by migration neoplastic cells in papillary dermis. Correspondingly, several experimental evidences documented structural functional rearrangement entire neoplasm that some way reflects atypia tumor cells. Lastly, must support proliferation survival outside normal epidermal-melanin units. task presumably mostly delegated fibroblasts ultimately self-autonomous review will discuss remodeling occurs epidermis during formation as well skin changes occur independently hyperproliferation having possible pro-tumoral features.

Language: Английский

Citations

5
Melanoma cells induce dedifferentiation and metabolic changes in adipocytes present in the tumor niche DOI Creative Commons
Aleksandra Simiczyjew, Justyna Wądzyńska, Katarzyna Pietraszek‐Gremplewicz

et al.

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: July 22, 2023

Abstract Background One of the factors that affect progression melanoma is tumor microenvironment, which consists cellular elements, extracellular matrix, acidification, and a hypoxic state. Adipocytes are one types cell present in niche localized deepest layer skin. However, relationship between fat cells remains unclear. Methods We assessed influence on adipocytes using an indirect coculture system. estimated level cancer-associated adipocyte (CAA) markers through quantitative PCR analysis. The fibroblastic phenotype CAAs was confirmed by staining western blotting lipid content detection LipidSpot analysis Oil Red O. expression proteins involved synthesis, delipidation, metabolic processes were or Lactate secretion established Lactate-Glo™ assay. Proteins secreted identified cytokine angiogenesis arrays. proliferation cocultured with XTT Statistical performed one-way ANOVA followed Tukey’s test GraphPad Prism 7 software. Results Obtained decreased levels leptin, adiponectin, resistin, FABP4. presented features, such as similar proteolytic pattern to 3T3L1 fibroblasts increased vimentin TGFβRIII. Melanoma led reduction CAAs, possibly downregulation synthesis pathways (lower FADS, SC4MOL, FASN) enhancement lipolysis (higher phosphorylation ERK STAT3). higher IL6 SerpinE1 produced less CCL2, CXCL1, angiogenic molecules. also showed changes comprising lactate enhanced production glucose, lactate, ion transporters. In addition, observed following resulted rate cancer cells. Conclusions adipocytes, might be related delipidation synthesis. Fibroblast-like may reason for accelerated

Language: Английский

Citations

11
The tumor immune microenvironment in primary cutaneous melanoma DOI Creative Commons
Catherine Zilberg, Angela L. Ferguson, J. Guy Lyons

et al.

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: Jan. 18, 2025

Abstract Melanoma is an immunogenic tumor. The melanoma tumor immune microenvironment (TIME) made up of a heterogenous mix both and non-immune cells as well multitude signaling molecules. interactions between cells, molecules affect progression therapeutic responses. Understanding the composition function TIME in primary cutaneous useful for prognostication decisions. This review provides overview components melanoma, their influence on clinical outcomes.

Language: Английский

Citations

0
MitoQ alleviates H2O2-induced mitochondrial dysfunction in keratinocytes through the Nrf2/PINK1 pathway DOI
Yan Zhao, Renxue Xiong,

Shiyu Jin

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116811 - 116811

Published: Feb. 1, 2025

Language: Английский

Citations

0
Melanoma-derived mediators can foster the premetastatic niche: crossroad to lymphatic metastasis DOI Creative Commons
Shankar Suman, Svetomir N. Markovic

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(9), P. 724 - 743

Published: Aug. 10, 2023

The natural history of advanced malignant melanoma demonstrates that, in most cases, widespread tumor dissemination is preceded by regional metastases involving tumor-draining lymph nodes [sentinel (SLNs)]. Under physiological conditions, LNs play a central role immunosurveillance to non-self-antigens which they are exposed via afferent lymph. dysfunctional immunity SLNs mediated secretory factors that allow the survival metastatic cells within LN creating premetastatic niche (PMN). Recent studies outline altered microenvironment shaped mediators. Here, we discuss involved subverting and remodeling highlight emerging therapeutic strategies reinvigorate antitumoral SLNs.

Language: Английский

Citations

10
Characterization of two melanoma cell lines resistant to BRAF/MEK inhibitors (vemurafenib and cobimetinib) DOI Creative Commons
Magdalena Kot, Aleksandra Simiczyjew, Justyna Wądzyńska

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 23, 2024

Abstract Background BRAF (v-raf murine sarcoma viral oncogene homolog B1)/MEK (mitogen-activated protein kinase kinase) inhibitors are used for melanoma treatment. Unfortunately, patients treated with this combined therapy develop resistance to treatment quite quickly, but the mechanisms underlying phenomenon not yet fully understood. Here, we report and characterize two cell lines (WM9 Hs294T) resistant (vemurafenib) MEK (cobimetinib) inhibitors. Methods Cell viability was assessed via XTT test. The level of selected proteins as well activation signaling pathways were evaluated using Western blotting. expression chosen genes by RT-PCR. distribution cycle phases analyzed flow cytometry, confocal microscopy take photos spheroids. composition cytokines secreted cells determined a human cytokine array. Results had increased survival ERK in presence BRAF/MEK IC 50 values these over 1000 times higher than controls. Resistant also exhibited elevated AKT, p38, JNK EGFR, ErbB2, MET, PDGFRβ receptors reduced ErbB3 receptor. Furthermore, demonstrated encoding involved drug transport metabolism. features epithelial-mesenchymal transition cancer stem proliferation rate secretion. Conclusions In summary, work describes BRAF/MEK-inhibitor-resistant cells, allowing better understanding resistance. results may thus contribute development new, more effective therapeutic strategies.

Language: Английский

Citations

1
The impact of cellular elements of TME on melanoma biology and its sensitivity to EGFR and MET targeted therapy DOI Creative Commons
Justyna Wądzyńska, Aleksandra Simiczyjew, Katarzyna Pietraszek‐Gremplewicz

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2023, Volume and Issue: 1870(7), P. 119549 - 119549

Published: July 27, 2023

Microenvironment of the melanoma consists cellular elements like fibroblasts, adipocytes, and keratinocytes as well extracellular matrix physicochemical conditions. In our previous research, we have established that influences strongly above mentioned cells present in tumor niche recruits them to support cancer progression. this work, evaluated impact cancer-associated cells, namely fibroblasts (CAFs), adipocytes (CAAs), (CAKs) on proliferation, signaling pathways activation, metabolism effectiveness used anti-cancer therapy. Obtained results indicated elevated phosphorylation STAT3, upregulated GLUT1 GLUT3 downregulated MCT-1 expression level under influence all examined niche. The proliferation was increased after co-culture with CAFs CAKs, while epithelial-mesenchymal transition markers' raised presence CAAs. perilipin 2 lipid content Moreover, CYP1A1, gene encoding drug metabolizing protein, co-cultured CAKs prompted us verify previously proposed by anti-melanoma therapy based combination EGFR MET inhibitors. indicate designed is still efficient, even if keratinocytes, are vicinity.

Language: Английский

Citations

2
Network Inference from Cancer and Epithelial Cell Co-Culture Reveal Microenvironmental Configurations That Drives Population Dynamics DOI Open Access
Alexandre Sarmento Queiroga, Mauro César Cafundó Morais, Beatriz Stransky

et al.

Published: Nov. 7, 2023

Human keratinocytes and melanoma can stick together to form clusters after eight days in co-culture. As dynamic system concepts, one consider cluster formation as the attractor, cell seeding initial condition, density change over time a path within basin of attraction. Herein, Cellular Automata, which is class Agent-Based Models, Boolean Networks are discrete modeling methods used population dynamics such that running cellular automata backward reveals an underlying network terms attraction, also known global dynamics. Thus, we hypothesize estimate local agent-based model from attraction boolean network. Here, propose approach estimating these rules, consists comparing states each state transition reaching consensus among transitions belonging The objectives this study are: (1) infer co-culture growth curve; (2) rules models; (3) implement spatial simulations. binarization curve shows high four days; estimated were compatible with proliferation migration agreement literature, so had individual for survival death. Spatial exhibit higher neighborhoods where present; chance keratinocyte increases until fourth day, then decreases, probability substantially cells low capacity die free space those ones. Our suggests attractor induced mainly by increase survival. has potential offer valuable clues about microenvironmental interactions or configurations drive

Language: Английский

Citations

2
Identification of genomic-wide genetic links between cutaneous melanoma and obesity-related physical traits via cFDR DOI
Lin Shen,

Runnan Shen,

Jingqian Huang

et al.

Genes & Genomics, Journal Year: 2023, Volume and Issue: 45(12), P. 1549 - 1562

Published: Sept. 28, 2023

Language: Английский

Citations

0
Network Inference from Cancer and Epithelial Cell Co-Culture Reveal Microenvironmental Configurations That Drives Population Dynamics DOI Open Access
Alexandre Sarmento Queiroga, Mauro César Cafundó Morais, Beatriz Stransky

et al.

Published: Oct. 25, 2023

Cellular Automata and Boolean Networks are generalizations of one another because algorithms to compute the preimage cellular automata reveal underlying network, i.e., global dynamics in terms basins attraction. Therefore, we hypothesize can local from basin attraction an inferred boolean network. Our motivation was observation that human keratinocytes melanoma stick together form clusters after eight days co-culture. This cluster formation would be attractor population dynamics, cell seeding initial condition Hence, propose a method estimate rules automata, which consist comparing density states within each state transition reaching consensus among transitions belonging aim: (1) infer network \emph{in vitro} co-culture growth curve; (2) automata; (3) implement for spatial simulations. The binarization curve shows high four days; estimated were compatible with proliferation migration agreement experimental observations. Spatial that: exhibit higher neighborhoods where is present; chance keratinocyte increases until fourth day, but probability survival increases; space freed cells maximum capacity through compensated by death. approach suggests induced increase survival, as well balance death concerning melanoma. has potential offer valuable clues about microenvironmental interactions or configurations drive dynamics.

Language: Английский

Citations

0