Comprehensive investigation of matrix metalloproteinases in skin cutaneous melanoma: diagnostic, prognostic, and therapeutic insights DOI Creative Commons

Liang-Hong Wu,

Chenxiaoxiao Liu,

Weicai Hu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 16, 2025

The dysregulation of matrix metalloproteinases (MMPs) in skin cutaneous melanoma (SKCM) represents a critical aspect tumorigenesis. In this study, we investigated the diagnostic, prognostic, and therapeutic aspects MMPs SKCM. Thirteen SKCM cell lines seven normal were cultured under standard conditions for experimental analyses. RNA DNA extracted, followed by RT-qPCR to assess MMP expression promoter methylation analysis determine levels. Functional assays, including proliferation, colony formation, wound healing, conducted post-MMP7 knockdown using siRNA A375 cells. Databases like GEPIA2, HPA, MEXPRESS, miRNet employed expression, survival, methylation, miRNA-mRNA network We landscape lines, revealing significant (p-value < 0.05) up-regulation MMP1, MMP7, MMP9, MMP10, MMP11, MMP12, MMP13, MMP14, MMP25, alongside down-regulation MMP2, MMP3, MMP21. Furthermore, our demonstrated inverse correlation between levels status, suggesting potential regulatory role dysregulation. Notably, MMP14 exhibited associations with overall survival patients, emphasizing their prognostic significance. Additionally, Receiver operating characteristic (ROC) curve highlighted diagnostic distinguishing from individuals. Subsequent validation across multiple cohorts confirmed elevated tissues, particularly advanced disease stages, further tumor progression. elucidated pathways involving miR-22-3p, which targets genes Our findings also revealed immune modulation, drug sensitivity, functional states Lastly, MMP7 cells significantly impacted several characteristics, healing. highlight These could serve as biomarkers early detection therapy. Future efforts should focus on preclinical clinical translate these insights into personalized strategies.

Language: Английский

Therapeutic Applications of Nanomedicine: Recent Developments and Future Perspectives DOI Creative Commons
Farah Rehan, Mingjie Zhang, Jun Fang

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(9), P. 2073 - 2073

Published: April 30, 2024

The concept of nanomedicine has evolved significantly in recent decades, leveraging the unique phenomenon known as enhanced permeability and retention (EPR) effect. This facilitated major advancements targeted drug delivery, imaging, individualized therapy through integration nanotechnology principles into medicine. Numerous nanomedicines have been developed applied for disease treatment, with a particular focus on cancer therapy. Recently, utilized various advanced fields, including diagnosis, vaccines, immunotherapy, gene tissue engineering. Multifunctional facilitate concurrent medication therapeutic monitoring, allowing immediate responses personalized treatment plans. review concerns advancement nanomaterials their potential applications biological medical fields. Along this, we also mention clinical translations challenges that is currently facing to overcome translation barrier.

Language: Английский

Citations

23
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

16
A surgical orthotopic xenograft approach with immune response for colorectal cancer research DOI Creative Commons
Xiaoying Hou, Xiaoxuan Li, Fang Qian

et al.

Animal Models and Experimental Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract The high morbidity and mortality of colorectal cancer (CRC) is a major challenge in clinical practice. Although series alternative research models CRC have been developed, appropriate orthotopic animal that reproduce the specific response as well pathophysiological immune features are still lacking. In current study, we constructed xenograft model by implanting tumor tubes at colorectum mice monitored development using bioluminescence imaging. This successfully recapitulates chemotherapy efficacy, including reduced total flux, weight, expression Ki67 after treatment first‐line regime (FOLFOX: oxaliplatin 5‐fluorouracil/calcium folinate). also reproduced immunosuppressive effect FOLFOX, indicated decreased infiltration macrophages increased Treg cells tumor. Additionally, approach may be applied immunodeficient NCG/NSG for constructing patient‐derived xenografts, being used precision medicine drug evaluation. We believe successful surgical deserves to popularized, which will provide convenient efficient platform in‐depth mechanism exploration preclinical

Language: Английский

Citations

2
The next frontier in immunotherapy: potential and challenges of CAR-macrophages DOI Creative Commons
Jing Li,

Ping Chen,

Wenxue Ma

et al.

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 5, 2024

Abstract Chimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers promising approach to target and eradicate tumor cells by utilizing macrophages’ phagocytic antigen-presenting abilities. However, challenges such as the complex microenvironment (TME), variability expression, immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of action, optimal construct designs, interactions within TME. It also delves into ex vivo manufacturing CAR-MΦ, discussing autologous allogeneic sources importance stringent quality control. The potential synergies integrating with existing cancer like checkpoint inhibitors conventional chemotherapeutics are examined highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways scrutinized alongside established protocols cells, identifying unique considerations essential clinical trials market approval. Proposed safety monitoring frameworks aim manage adverse events, cytokine release syndrome, crucial patient safety. Consolidating current research insights, this seeks refine therapeutic applications, overcome barriers, suggest future directions transition from experimental platforms standard care options.

Language: Английский

Citations

12
Combined targeting of senescent cells and senescent macrophages: A new idea for integrated treatment of lung cancer DOI
Ming Gu, Yang Liu, Wenhui Zheng

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 106-107, P. 43 - 57

Published: Aug. 29, 2024

Language: Английский

Citations

11
It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma DOI Creative Commons

Christin Knickmeier,

Gaetan Aime Noubissi Nzeteu, Bernhard F. Gibbs

et al.

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

Published: Jan. 31, 2025

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by an extremely poor prognosis and limited therapeutic options. Central to progression immune evasion PDAC is tumor (immune) microenvironment (TIME), where checkpoint proteins such as galectin-9 (Gal-9) play pivotal roles. Gal-9 significantly contributes immunosuppressive milieu interacting with various cells, T macrophages, myeloid-derived suppressor cells (MDSCs). These interactions suppress anti-tumor immunity, thus facilitating growth metastasis. This review comprehensively examines multifaceted role in TIME PDAC, detailing its mechanisms action, including induction regulatory polarization tumor-associated modulation apoptotic pathways via Tim-3 caspase activation. The potential targeting Gal-9, either alone or combination other inhibitors anti-PD-L1, also discussed, highlighting preclinical findings that suggest promising avenues for enhancing responses. By elucidating complex biological activities within TIME, this underscores importance innovative strategies aimed at mitigating effects PDAC.

Language: Английский

Citations

1
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 DOI Creative Commons
Francesco Verona, Sebastiano Di Bella,

Roberto Schirano

et al.

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

Citations

1
Tumor secretome shapes the immune landscape during cancer progression DOI Creative Commons
Jianqiang Yang, Sijia Tang, Nabil F. Saba

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 10, 2025

Language: Английский

Citations

1
Breast cancer stem cells convert anti-tumor CD4+ T cells to pro-tumor T regulatory cells: Potential role of exosomal FOXP3 DOI
Udit Basak, Sourio Chakraborty, Sumon Mukherjee

et al.

Cellular Immunology, Journal Year: 2025, Volume and Issue: 409-410, P. 104931 - 104931

Published: Feb. 20, 2025

Language: Английский

Citations

1
Irradiated microparticles suppress prostate cancer by tumor microenvironment reprogramming and ferroptosis DOI Creative Commons

Zihan Deng,

Binghui Li, Muyang Yang

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 5, 2024

Abstract Immunogenic cell death (ICD) plays a crucial role in triggering the antitumor immune response tumor microenvironment (TME). Recently, considerable attention has been dedicated to ferroptosis, type of ICD that is induced by intracellular iron and demonstrated change desert status TME. However, among cancers are characterized an desert, such as prostate cancer, strategies for inducing high levels ferroptosis remain limited. Radiated cell-derived microparticles (RMPs) radiotherapy mimetics have shown activate cGAS-STING pathway, induce inhibit M2 macrophage polarization. RMPs can also act carriers agents with biocompatibility. In present study, we designed therapeutic system wherein inducer RSL-3 was loaded into RMPs, which were tested vitro vivo carcinoma models established using RM-1 cells. The apoptosis CT20 peptide (CT20p) added aggravate ferroptosis. Our results showed RSL-3- CT20p-loaded (RC@RMPs) led Moreover, CT20p had synergistic effect on promoting reactive oxygen species (ROS) production, lipid hydroperoxide mitochondrial instability. RC@RMPs elevated dendritic (DC) expression MHCII, CD80, CD86 facilitated M1 subcutaneously transplanted model mice, inhibited growth prolonged survival time via DC activation, reprogramming, enhancement CD8 + T infiltration, proinflammatory cytokine production tumor. combination treatment anti-PD-1 improved inhibition. This study provides strategy cancer immunotherapies. Graphical

Language: Английский

Citations

7