Signaling, cancer cell plasticity, and intratumor heterogeneity

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

Published: May 3, 2024

Abstract Cancer’s complexity is in part due to the presence of intratumor heterogeneity and dynamic nature cancer cell plasticity, which create substantial obstacles effective management. Variability within a tumor arises from existence diverse populations cells, impacting progression, spread, resistance treatments. At core this variability concept cellular plasticity - intrinsic ability cells alter their molecular identity reaction environmental genetic changes. This adaptability cornerstone cancer’s persistence making it formidable target for Emerging studies have emphasized critical role such fostering diversity, turn influences course disease effectiveness therapeutic strategies. The transformative involves network signal transduction pathways, notably those that drive epithelial-to-mesenchymal transition metabolic remodeling, shaping evolutionary path cells. Despite advancements, our understanding precise machinations signaling networks driving these changes still evolving, underscoring necessity further research. editorial presents series entitled “Signaling Cancer Cell Plasticity Intratumor Heterogeneity” Communication Signaling, dedicated unraveling complex processes proposing new avenues intervention.

Language: Английский

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The Roles of Myeloid Cells in Breast Cancer Progression

Advances in experimental medicine and biology, Journal Year: 2025, Volume and Issue: unknown, P. 397 - 412

Published: Jan. 1, 2025

Language: Английский

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Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 6, 2025

Cancer stem cells (CSCs) are a small subset within the tumor mass significantly contributing to cancer progression through dysregulation of various oncogenic pathways, driving growth, chemoresistance and metastasis formation. The aggressive behavior CSCs is guided by several intracellular signaling pathways such as WNT, NF-kappa-B, NOTCH, Hedgehog, JAK-STAT, PI3K/AKT1/MTOR, TGF/SMAD, PPAR MAPK kinases, well extracellular vesicles exosomes, molecules cytokines, chemokines, pro-angiogenetic growth factors, which finely regulate CSC phenotype. In this scenario, microenvironment (TME) key player in establishment permissive niche, where engage intricate communications with diverse immune cells. "oncogenic" mainly represented B T lymphocytes, NK cells, dendritic Among macrophages exhibit more plastic adaptable phenotype due their different subpopulations, characterized both immunosuppressive inflammatory phenotypes. Specifically, tumor-associated (TAMs) create an milieu production plethora paracrine factors (IL-6, IL-12, TNF-alpha, TGF-beta, CCL1, CCL18) promoting acquisition stem-like, invasive metastatic TAMs have demonstrated ability communicate via direct ligand/receptor (such CD90/CD11b, LSECtin/BTN3A3, EPHA4/Ephrin) interaction. On other hand, exhibited capacity influence creating favorable for progression. Interestingly, bidirectional TME leads epigenetic reprogramming sustains malignant transformation. Nowadays, integration biological computational data obtained cutting-edge technologies (single-cell RNA sequencing, spatial transcriptomics, trajectory analysis) has improved comprehension biunivocal multicellular dialogue, providing comprehensive view heterogeneity dynamics CSCs, uncovering alternative mechanisms evasion therapeutic resistance. Moreover, combination biology will lead development innovative target therapies dampening CSC-TME Here, we aim elucidate most recent insights on complex interactions specifically TAMs, tracing exhaustive scenario from primary

Language: Английский

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Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 22, 2024

Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of gastric mucosa. The pathogenesis GC intricately linked to tumor microenvironment within which reside. Tumor-associated macrophages (TAMs) primarily differentiate peripheral blood monocytes and can be broadly categorized into M1 M2 subtypes. M2-type TAMs have been shown promote growth, tissue remodeling, angiogenesis. Furthermore, they actively suppress acquired immunity, leading poorer prognosis reduced tolerance chemotherapy. Exosomes, contain myriad biologically active molecules including lipids, proteins, mRNA, noncoding RNAs, emerged as key mediators communication between TAMs. exchange these via exosomes markedly influence consequently impact progression. Recent studies elucidated correlation various clinicopathological parameters GC, such size, differentiation, infiltration depth, lymph node metastasis, TNM staging, highlighting pivotal role in development metastasis. In this review, we aim comprehensively examine bidirectional TAMs, implications alterations on immune escape, invasion, metastasis targeted therapeutic approaches for efficacy potential drug resistance strategies.

Language: Английский

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Targeting tumor‑associated macrophages: Critical players in tumor progression and therapeutic strategies (Review)

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 64(6)

Published: April 30, 2024

Tumor‑associated macrophages (TAMs) are essential components of the tumor microenvironment (TME) and display phenotypic heterogeneity plasticity associated with stimulation bioactive molecules within TME. TAMs predominantly exhibit tumor‑promoting phenotypes involved in progression, such as angiogenesis, metastasis, immunosuppression resistance to therapies. In addition, have potential regulate cytotoxic elimination phagocytosis cancer cells interact other immune engage innate adaptive systems. this context, targeting has been a popular area research therapy, comprehensive understanding complex role progression exploration macrophage‑based therapeutic approaches for future therapeutics against cancers. The present review provided updated overview function summarized recent advances TAM‑targeting strategies discussed obstacles perspectives therapies

Language: Английский

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The Role of TAMs in the Regulation of Tumor Cell Resistance to Chemotherapy

Critical Reviews™ in Oncogenesis, Journal Year: 2024, Volume and Issue: 29(4), P. 97 - 125

Published: Jan. 1, 2024

Tumor-associated macrophages (TAMs) are the predominant cell infiltrate in immunosuppressive tumor microenvironment (TME). TAMs central to fostering pro-inflammatory conditions, growth, metastasis, and inhibiting therapy responses. Many cancer patients innately refractory chemotherapy or develop resistance following initial treatments. There is a clinical correlation between level of TME chemoresistance. Hence, pivotal role contributing chemoresistance has garnered significant attention toward targeting reverse this resistance. A prerequisite for such an approach requires thorough understanding various underlying mechanisms by which inhibit response chemotherapeutic drugs. Such include enhancing drug efflux, regulating metabolism detoxification, supporting stem (CSCs) resistance, promoting epithelial-mesenchymal transition (EMT), penetration its metabolism, stimulating angiogenesis, impacting inhibitory STAT3/NF-κB survival pathways, releasing specific cytokines including TGF-β IL-10. Accordingly, several strategies have been developed overcome TAM-modulated These novel therapies that aim deplete TAMs, repolarize them anti-tumor M1-like phenotype, block recruitment monocytes into TME. Current results from TAM-targeted treatments unimpressive; however, use combination appears promising with radiotherapy, chemotherapy, chemokine receptor inhibitors, immunotherapy, loaded nanoparticles. The limitations these discussed.

Language: Английский

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The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 10, 2023

Chronic liver diseases from varying etiologies generally lead to fibrosis and cirrhosis. Among them, non-alcoholic fatty disease (NAFLD) affects roughly one-quarter of the world population, thus representing a major increasing public health burden. hepatocyte injury, inflammation (non-alcoholic steatohepatitis, NASH) are recognized soils for primary cancer, particularly hepatocellular carcinoma (HCC), being third most common cause cancer-related deaths worldwide. Despite recent advances in understanding, therapeutic options on pre-malignant malignant stages remain limited. Thus, there is an urgent need identify targetable disease-driving mechanisms development novel therapeutics. Monocytes macrophages comprise central, yet versatile component inflammatory response, fueling chronic initiation progression. Recent proteomic transcriptomic studies performed at singular cell levels revealed previously overlooked diversity macrophage subpopulations functions. Indeed, that encompass resident (also named Kupffer cells) monocyte-derived macrophages, can acquire variety phenotypes depending microenvironmental cues, exert manifold sometimes contradictory Those functions range modulating exacerbating tissue promoting exaggerating repair (i.e., parenchymal regeneration, cancer proliferation, angiogenesis, fibrosis). Due these central functions, represent attractive target treatment diseases. In this review, we discuss multifaceted contrary roles diseases, with particular focus NAFLD/NASH HCC. Moreover, potential approaches targeting macrophages.

Language: Английский

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M2‐like tumor‐associated macrophages promote epithelial–mesenchymal transition through the transforming growth factor β/Smad/zinc finger e‐box binding homeobox pathway with increased metastatic potential and tumor cell proliferation in lung squamous cell carcinoma

Cancer Science, Journal Year: 2023, Volume and Issue: 114(12), P. 4521 - 4534

Published: Oct. 8, 2023

Abstract Epithelial‑mesenchymal transition (EMT) promotes primary tumor progression toward a metastatic state. The role of tumor‐associated macrophages (TAMs) in inducing EMT lung squamous cell carcinoma (LUSC) remains unclear. We aimed to clarify the significance TAMs relation LUSC. collected 221 LUSC specimens from patients who had undergone surgery. Immunohistochemistry was performed evaluate M1‐like and M2‐like TAM distribution by E‐cadherin vimentin staining. Human lines (H226 EBC‐1) human monocyte line (THP‐1) were used for vitro experiments. polarization marker expression cells evaluated western blotting. biological behavior migration, invasion, proliferation assays. Immunohistochemical analysis showed that 166 (75.1%) tumors E‐cadherin‐positive 44 (19.9%) vimentin‐positive. density stroma significantly associated with positivity worse overall survival. Western blotting demonstrated higher levels CD163, CD206, vascular endothelial growth factor, transforming factor beta 1 (TGF‐β1) versus unstimulated macrophages. Furthermore, increased TGF‐β1 secretion confirmed ELISA. TAM‐co‐cultured H226 EBC‐1 exhibited (decreased E‐cadherin, vimentin). Regarding EMT‐activating transcriptional factors, phosphorylated Smad3 ZEB‐family proteins than parental cells. enhanced migration invasion capabilities improved proliferation. Overall, present study suggests can induce potential

Language: Английский

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Role of Tumor-Associated Macrophages in Cervical Cancer: Integrating Classical Perspectives with Recent Technological Advances

Life, Journal Year: 2024, Volume and Issue: 14(4), P. 443 - 443

Published: March 27, 2024

Tumor-associated macrophages (TAMs) play a pivotal role in the tumor microenvironment, influencing cancer progression and contributing to poor prognosis. However, cervical (CC), their significance involvement are relatively less studied than other gynecological cancers such as ovarian endometrial cancer. This review aims provide an overview of TAMs, covering origins phenotypes impact on CC progression, along with major TAM-targeted therapeutic approaches. Furthermore, we advocate for integration cutting-edge research methodologies, single-cell RNA sequencing spatial sequencing, enable in-depth comprehensive investigations into TAMs CC, which would be beneficial leading more personalized effective immunotherapy strategies patients CC.

Language: Английский

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Factors Determining Epithelial-Mesenchymal Transition in Cancer Progression

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8972 - 8972

Published: Aug. 17, 2024

Epithelial-mesenchymal transition (EMT) is a process in which an epithelial cell undergoes multiple modifications, acquiring both morphological and functional characteristics of mesenchymal cell. This dynamic initiated by various inducing signals that activate numerous signaling pathways, leading to the stimulation transcription factors. EMT plays significant role cancer progression, such as metastasis tumor heterogeneity, well drug resistance. In this article, we studied molecular mechanisms, epigenetic regulation, cellular plasticity EMT, microenvironmental factors influencing process. We included vivo vitro models investigation clinical implications use curing oncological patients targeting its therapies. Additionally, review concludes with future directions challenges wide field EMT.

Language: Английский

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