Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 30, 2024

In the realm of cancer research, tumor microenvironment (TME) plays a crucial role in initiation and progression, shaped by complex interactions between cells surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted various cellular constituents within TME, including immune cells, cancer-associated fibroblasts, themselves. These cytokines facilitate intricate communication networks that significantly influence initiation, metastasis, suppression. Pyroptosis contributes to TME remodeling promoting release pro-inflammatory sustaining chronic inflammation, impacting processes such escape angiogenesis. However, challenges remain due interplay among cytokines, pyroptosis, along with dual effects pyroptosis on progression therapy-related complications like cytokine syndrome. Unraveling these complexities could strategies balance inflammatory responses while minimizing tissue damage during therapy. This review delves into crosstalk elucidating their contribution metastasis. By synthesizing emerging therapeutic targets innovative technologies concerning this aims provide novel insights enhance treatment outcomes for patients.

Language: Английский

---

Mitochondria‐derived vesicles: A promising and potential target for tumour therapy

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(5)

Published: May 1, 2025

Abstract Mitochondria‐derived vesicles (MDVs) participate in early cellular defence mechanisms initiated response to mitochondrial damage. They maintain quality control (MQC) by clearing damaged components, thereby ensuring the normal functioning of processes. This process is crucial for cell survival and health, as mitochondria are energy factories cells, their damage can cause dysfunction even death. Recent studies have shown that MDVs not only health but also a significant impact on tumour progression. selectively encapsulate transport proteins under oxidative stress reduce adverse effects which may promote proliferation cells. Furthermore, it has been indicated after cells experience mild stress, number significantly increases within 2–6 h, whereas mitophagy, mitochondria, occurs 12–24 h later. suggests play critical role Moreover, intercellular communication, specifically microenvironment. carry transmit various bioactive molecules, such proteins, nucleic acids, lipids, regulate cell's growth, invasion, metastasis. communication facilitate spread metastasis, making potential therapeutic target. Advances MDV research identified novel biomarkers, clarified regulatory mechanisms, provided evidence clinical use. These breakthroughs pave way MDV‐targeted therapies, offering improved treatment alternatives cancer patients. Further identify MDVs' development elucidate future horizons.

Language: Английский

---

Macrophage-dormant disseminated cancer cell interactions: valuable implications for metastasis and prevention

Science Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

---

Research hotspots and frontiers in the tumor microenvironment of colorectal cancer: a bibliometric study from 2014 to 2024

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 5, 2025

Background Colorectal cancer (CRC) is the second leading cause of deaths globally, which poses a heavy burden on our healthcare and economy. In recent years, increasing researches suggest that tumor microenvironment (TME) influences onset, progression, metastasis, treatment. This has become popular direction for researching attacking cancer. However, to date, there no bibliometric analysis colorectal from 2014 2024. study aims provide comprehensive picture current research status, hotspots, future trends in this field perspective. Methods study, publications about 2024 were searched based Web Science Core Collection database. Then we analyzed visualized data using CiteSpace, VOSviewer, bibliometrix package, Microsoft Excel 2019. Results A total 748 included number entered period rapid growth after China United States are major collaboration centers field. Elkord, Eyad most prolific author, Frontiers Immunology journal published papers TME CRC. addition, keyword cluster showed immune checkpoint inhibitors, cancer-associated fibroblasts, macrophage polarization, intestinal microbiota, liver drug resistance, scRNA-seq, etc. may be hotspots Conclusions developmental stage, strengthening international cooperation can help drive forward. The main components signaling TME, CRC immunotherapy, new techniques hot directions domain. Our findings will scholars with an up-to-date perspective state research,

Language: Английский

---

Comprehensive pan-cancer analysis of LAMA3: implications for prognosis and immunotherapy

American Journal of Translational Research, Journal Year: 2025, Volume and Issue: 17(2), P. 1200 - 1222

Published: Jan. 1, 2025

Laminin subunit alpha 3 (LAMA3) has been implicated in various cellular processes relevant to cancer progression, including cell proliferation, migration, and adhesion. In this study, we explored the expression, prognostic significance, functional role of LAMA3 across multiple types. The silico analyses involve using bioinformatics tools databases, such as Cancer Genome Atlas (TCGA), TIMER2.0, GEPIA2, UALCAN, Kaplan-Meier (KM) plotter, GENT2, Human Protein (HPA), OncoDB, Gene Set Analysis (GSCA), TISIDB. vitro include culture, gene knockdown, assays for colony formation, wound healing. Pan-cancer analysis revealed significant variations with upregulation observed cancers pancreatic adenocarcinoma (PAAD) stomach (STAD), downregulation breast (BRCA) colon (COAD). Prognostic indicated high expression correlated poor overall survival (OS) PAAD STAD, whereas low was associated adverse outcomes BRCA. Validation confirmed differential localized primarily endoplasmic reticulum. clinical features BRCA, PAAD, STAD showed consistent trends different stages, races, age groups. Additionally, mutational copy number (CNVs) prevalent heterozygous amplifications deletions STAD. Promoter methylation inversely although were unaffected. Protein-protein interaction (PPI) enrichment LAMA3's involvement ECM-receptor interactions PI3K-Akt signaling, pathways critical cancer. Finally, following knockdown HT-29 cells demonstrated reduced healing, implicating tumor growth metastasis. Overall, these findings suggest that plays a multifaceted tumorigenesis holds potential biomarker therapeutic target cancers.

Language: Английский

---

Editorial: Molecular mechanisms and therapeutic targets of cancer metastasis and therapy resistance

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 5, 2025

from the primary tumor site to distant organs, where they form secondary foci.The occurrence of metastasis involves complex cellular signaling pathways and changes in microenvironment (1). Tumor resistance, especially chemotherapy, targeted therapy, immunotherapy, significantly impacts treatment efficacy, resulting recurrence cancer progression. To improve survival quality life patients, it is urgent understand molecular mechanisms drug resistance identify new therapeutic targets.Tumor a multi-step process, involving detachment cells, invasion, dissemination through blood or lymphatic systems, growth organs. Epithelial-Mesenchymal Transition (EMT) critical process which cells acquire invasive metastatic potential (2,3). The (e.g. cancer-associated fibroblasts, etc.) immune tumor-associated macrophages, also participate (4).Additionally, angiogenesis an important condition for metastasis. Deregulation Cuproptosis has been linked metastasis, recent review by Wang et al., unbalanced levels copper promote angiogenesis, enabling cell spread (Frontiers oncology. 2023;13:1288504.). Moreover, could degrade extracellular matrix secretion metalloproteinases other enzymes, creating conditions crossing tissue barriers (5). Some molecules are involved cells. Adhesion integrins, cadherins, etc.), factors cytokines epidermal factor, platelet-derived Wnt/βcatenin pathway, PI3K/Akt/mTOR pathway play key roles (6,7). Min al. recently reviewed impact adhesion-associated molecule Desmoglein-2 (DSG2) on adhesion, migration, vasculogenic mimicry. More importantly, proposed that pro-tumorigenic anti-tumorigenic function DSG2 context dependent 2023;13:1327478.).Tumor significant challenge treatment, as employ various render drugs ineffective reduce their efficacy. P-glycoprotein, multidrug resistance-associated proteins family, breast protein examples efflux pumps expel chemotherapy (8). Gene mutations including PIK3CA, KRAS, EGFR, p53 OCT4 have related phenotype (9). undergo metabolic reprogramming increasing antioxidant enhance (10,11). DNA methylation, histone modification noncoding RNAs regulation alter gene expression leading escaping drug-induced death (12). repair capabilities resist damage induced drugs. Kaljunen found inactivation Fanconi anemia reverse prostate during DNA-damaging line-specific manner 2023;13:1260826.). apoptotic would ability lead (13). stem small population within possess self-renewal multi-lineage differentiation capabilities, (14). High heterogeneity makes vary sensitivity with some potentially harboring genetic phenotypic features (15). Immune checkpoint inhibitors PD-1/PD-L1 nivolumab, pembrolizumab, system attack tumors, intensively investigated several cancers (17). Immunotherapy targeting specific antigens (e.g., HPV vaccines) boosts memory prevent (18). Taking into consideration, combining multiple approaches (such immunotherapy chemotherapy) become strategy. target different provide comprehensive against strategy.Tumor two major challenges treatment. Currently, progress made research targets resistance. In future, further needed discover more effective develop precise, efficient, low-toxicity strategies outcomes rates patients. Combination therapies, such therapies radiotherapy, may be direction overcome deserve in-depth exploration. Additionally, continuous development technologies CRISPR editing, single-cell sequencing), we expect obtain precise strategies. By continuously delving open up avenues, improving

Language: Английский

---

Current advancement of immune function paradox of tumour-infiltrating cells and their immunotherapeutic targets: a mini-review

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

---

The Coincidence of Ovarian Endometrioma with Paratubal Leydig Cell Nodules: A Case Report and Literature Review

Diagnostics, Journal Year: 2025, Volume and Issue: 15(6), P. 703 - 703

Published: March 12, 2025

Background and Clinical Significance: Paratubal Leydig cell nodules are rare incidental findings that present diagnostic challenges. Case Presentation: A 45-year-old female with a history of hypertension diabetes mellitus presented fever chills following an episode severe dysmenorrhea menorrhagia. The patient reported heavy menstrual bleeding, persisting for 2–3 years. Physical examination revealed erythema the perineum whitish vaginal discharge, no cervical lesions. Imaging 15 cm right ovarian cyst. Laboratory investigations showed elevated C-reactive protein (6.37 mg/L) CA125 (88.82 U/mL) levels, whereas other tumor markers were within normal limits. pelvic ultrasound retroverted uterus large mass suggestive malignancy. underwent salpingo-oophorectomy, during which adherent to sidewall was excised. Histopathological endometriotic cyst endometrial glandular epithelium positive estrogen receptor focal mucinous metaplasia. CD10-positive stromal cells paratubal cysts also observed. Additionally, small originated from hilum identified confirmed by staining inhibin, calretinin, androgen receptors, as well negative staining. postoperative recovery uneventful, at five-week follow-up, patient’s hormonal levels normal, there complications. Conclusions: This case highlights importance thorough histopathological evaluation in managing masses potential coexistence benign pathological entities, such tumors.

Language: Английский

---

MYC: Master Regulator of Cell Death and Tumor Progression

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

MYC gene has become one of the most investigated oncogenes for regulating programmed cell death and tumor growth. is a transcription factor that regulates expression numerous genes involved in critical cellular processes, such as metabolism, stress response, proliferation. However, its dysfunction, often caused by amplifications or translocations, makes it potent oncogenic driver, contributing to uncontrolled growth, angiogenesis, invasiveness, metastasis. Paradoxically, can promote both survival elimination through activation apoptotic mechanisms, creating delicate balance between death. This chapter explores dual role regulator life death, analyzing molecular mechanisms determine activity different biological contexts. The main pathways controlled MYC, contribution plasticity, interactions with other suppressors will be discussed. Finally, emerging therapeutic strategies aimed at targeting regulatory networks reviewed, along challenges translating this knowledge into clinical interventions. A thorough understanding biology crucial develop innovative therapies improve treatment aggressive resistant tumors.

Language: Английский

---

Targeting the TLK1-MK5 Axis Suppresses Prostate Cancer Metastasis

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1187 - 1187

Published: March 31, 2025

Background: The spread of metastatic prostate cancer (PCa) is responsible for the majority PCa-related deaths, yet precise mechanisms driving this process remain unclear. We have identified a novel interaction between two distinct promotility factors, tousled-like kinase 1 (TLK1) and MAPK-activated protein 5 (MK5), which triggers signaling cascade that promotes metastasis. In PCa, TLK1-MK5 pathway may play critical role, as androgen deprivation therapy (ADT) has been linked to increased expression both TLK1 MK5 in patients with poor survival. Objectives: study, we directly examined effects disrupting TLK1>MK5 axis on motility, invasiveness, potential PCa cells. Methods: To establish this, used pharmacologic systemic approaches genetically engineered mouse models use IVIS. Results: results targeting support notion essential cells development age-related metastases.

Language: Английский

---