CHEMOTHERAPY-INDUCED PDL-1 EXPRESSION IN CANCER-ASSOCIATED FIBROBLASTS PROMOTES CHEMORESISTANCE IN NSCLC DOI Open Access

Gayathri Heenatigala Palliyage

Published: Jan. 1, 2023

A cure for cancer is out of reach most patients due to chemoresistance. Cancer-associated fibroblasts (CAFs), one the abundant types stromal cells in tumor microenvironment, are known provide functional and structural support progression. These also play a role chemoresistance, but detailed understanding process, particularly chemoresistant lung cancer, lacking. In this study, we investigated programmed death-ligand 1 (PDL-1) as potential biomarker CAF-induced chemoresistance evaluated its underlying mechanisms non-small cell (NSCLC). We demonstrated that chemotherapy-stimulated CAFs promoted tumorigenic stem cell-like properties NSCLC cells, which could contribute their Subsequently, revealed PDL-1 expression upregulated chemotherapy-treated associated with poor prognosis. Silencing suppressed CAFs’ ability promote invasiveness favoring uncovered an upregulation led increase hepatocyte growth factor (HGF) secretion from CAFs, stimulates progression, invasion, stemness while inhibiting apoptosis. Taken together, our results show PDL-1-positive modulate by secreting elevated HGF, thereby promoting Our finding supports chemotherapy response drug delivery therapeutic target NSCLC.

Language: Английский

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
IFNγ and TNFα drive an inflammatory secretion profile in cancer‐associated fibroblasts from human non‐small cell lung cancer DOI Creative Commons
Lilian Koppensteiner, Layla Mathieson,

LYNNE NEILSON

et al.

FEBS Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Cancer‐associated fibroblasts (CAFs) are the dominant nonmalignant component of tumour microenvironment (TME). CAFs demonstrate a high level inter‐ and intra‐tumour heterogeneity in solid tumours, though drivers CAF subpopulations not fully understood. Here, we that non‐small cell lung cancer (NSCLC) patient‐derived upregulate secretion inflammatory cytokines (IL6, LIF, IL33, GM‐CSF, IL1ra) chemokines (CCL2, CCL3, CCL4, CCL20, CXCL8, CXCL9, CXCL10, CXCL11) response to vitro co‐culture with anti‐CD3/anti‐CD28‐stimulated peripheral blood mononuclear cells (PBMCs) via IFNγ TNFα. Furthermore, T‐cell‐derived inhibits CXCL12 by . Our results highlight ability T‐cell effector modulate secretome NSCLC.

Language: Английский

Citations

1
Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors DOI Creative Commons

Longyang Cao,

Hong Ouyang

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 23, 2024

Gastrointestinal (GI) tumors are a significant global health threat, with high rates of morbidity and mortality. Exosomes contain various biologically active molecules like nucleic acids, proteins, lipids can serve as messengers for intercellular communication. They play critical roles in the exchange information between tumor cells microenvironment (TME). The TME consists mesenchymal components extracellular matrix (ECM), fibroblasts being most abundant cell type mesenchyme. Cancer-associated (CAFs) derived from normal stem that activated TME. CAFs secrete exosomes to modulate proliferation, invasion, migration, drug resistance, other biological processes tumors. Additionally, manipulate function behavior through direct cell-cell interactions. This review provides summary crosstalk GI exosomes, along potential underlying mechanisms.

Language: Английский

Citations

8
Cancer-associated fibroblasts promote gastric cancer cell proliferation by paracrine FGF2-driven ribosome biogenesis DOI
Dandan Li, Pan Huang,

Lingyun Xia

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111836 - 111836

Published: March 12, 2024

Language: Английский

Citations

7
A novel TGFbeta/TGILR axis mediates crosstalk between cancer-associated fibroblasts and tumor cells to drive gastric cancer progression DOI Creative Commons

Shanshan Qin,

Qiwei Guo, Yue Liu

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(5)

Published: May 28, 2024

Abstract Transforming growth factor beta (TGFβ) signaling plays a critical role in tumorigenesis and metastasis. However, little is known about the biological function of TGFbeta-induced lncRNA cancer. In this study, we discovered novel TG Fbeta- i nduced l nc R NA, termed TGILR , whose cancer remains unknown to date. expression was directly activated by canonical TGFbeta/SMAD3 axis, activation highly conserved Clinical analysis showed that overexpression significant correlation with lymph node metastasis poor survival an independent prognostic gastric (GC). Depletion caused obvious inhibitory effect on GC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) vitro vivo. More importantly, demonstrated TGFbeta overactivated due cancer-associated fibroblast (CAF) infiltration. Mechanistically, increased level CAF-secreted activates signaling, leading cells. Meanwhile, inhibited microRNA biogenesis miR-1306 miR-33a interacting TARBP2 reducing its protein stability, thereby promoting progression via TCF4-mediated EMT signaling. conclusion, CAF infiltration drives through activating TGFbeta/TGILR axis. Targeted blocking CAF-derived should be promising anticancer strategy GC.

Language: Английский

Citations

7
Characterization of preovulatory follicular fluid secretome and its effects on equine oocytes during in vitro maturation DOI Creative Commons
Marcos Luis‐Calero, Federica Marinaro, Pablo Fernández‐Hernández

et al.

Research in Veterinary Science, Journal Year: 2024, Volume and Issue: 171, P. 105222 - 105222

Published: March 11, 2024

In vitro maturation (IVM) of oocytes is clinically used in horses to produce blastocysts but current conditions for are suboptimal. We analyzed the composition equine preovulatory follicular fluid (FF) secretome and tested its effects on meiotic competence gene expression subjected IVM. Preovulatory FF was obtained, concentrated using ultrafiltration with cut-off 10 kDa, stored at −80 °C. The metabolic proteomic analyzed, ultrastructural assessed by cryo-transmission microscopy. Oocytes obtained post-mortem or ovum pick up (OPU) were IVM absence (control) presence 20 40 μg/ml (S20 S40) secretome. then chromatin configuration snap frozen analysis. Proteomic analysis detected 255 proteins Equus caballus database, mostly related complement cascade cholesterol metabolism. Metabolomic yielded 14 metabolites electron microscopy revealed extracellular vesicles (EVs). No significant differences rates among treatments. However, GDF9 BMP15 significantly increased OPU-derived compared (fold increase ± SEM: 9.4 0.1 vs. 1 0.5 9.9 0.3 GDF9, respectively; p < 0.05). Secretome addition TNFAIP6 S40 regardless oocyte source. Further research necessary fully understand whether influences developmental oocytes.

Language: Английский

Citations

4
Cancer-associated fibroblasts promote enzalutamide resistance and PD-L1 expression in prostate cancer through CCL5-CCR5 paracrine axis DOI Creative Commons
Zhi Xiong,

Shun-Li Yu,

Zhaoxiang Xie

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(5), P. 109674 - 109674

Published: April 4, 2024

Cancer-associated fibroblasts (CAFs) have been shown to play a key role in prostate cancer treatment resistance, but the of CAFs initial course enzalutamide therapy for remains unclear. Our research revealed that secrete CCL5, which promotes upregulation androgen receptor (AR) expression cells, leading resistance therapy. Furthermore, CCL5 also enhances tumor programmed death-ligand 1 (PD-L1), resulting immune escape. Mechanistically, binds CCR5 on cells and activates AKT signaling pathway, AR PD-L1. The antagonist maraviroc inhibit mediated pathway can effectively reduce PD-L1, improve efficacy enzalutamide. This study highlights promising therapeutic approach targeting CCL5-CCR5 effectiveness

Language: Английский

Citations

4
Influence of stromal neural crest progenitor cells on neuroblastoma radioresistance DOI
Carlos Huertas-Castaño, Laura Martínez-López, P. Cabrera

et al.

International Journal of Radiation Biology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 11

Published: Jan. 3, 2025

A substantial proportion of children with high risk Neuroblastoma die within the first 5 years post-diagnosis despite complex treatment applied. In recent years, tumor environment has been revealed as key factor for cancer efficacy. this sense, non-tumorigenic Neural Crest progenitor cells from patients, have described part stroma, promoting growth and contributing to mesenchyme formation. paper we wanted study radiobiological behavior these (NB14t) how they influence tumorigenic neuroblasts after radiotherapy.

Language: Английский

Citations

0
Decoding the MMP14 Integrin Link: Key Player in the Secretome Landscape DOI Creative Commons
Stephan Niland, Johannes A. Eble

Matrix Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Rapid progress has been made in the exciting field of secretome research health and disease. The tumor secretome, which is a significant proportion proteome, secreted into extracellular space to promote intercellular communication thus progression. Among many molecules integrins matrix metalloproteinase 14 (MMP14) stand out as interplay adhesion proteolysis drives invasion. Integrins serve mechanosensors that mediate contact cells with scaffold are significantly involved precise positioning activity control membrane-bound collagenase MMP14. As proteinase, MMP14 influences modifies itself. While MT-MMPs membrane bound, but can be released therefore border crossers between cell surface not constitutively cell-bound, its binding other receptors stringently regulated process. To understand mutual interactions detail, we first summarize structure function how it at enzymatic cellular level. In particular, include proteolytic cleavage themselves by We then review biochemical, biological physiological effects on composition associated functions when either bound membrane, or located microvesicles, proteolytically shed non-membrane-bound ectodomain. Novel methods proteomics, including analysis extravesicular vesicles, new for quantification will provide diagnostic tools. modification especially MMP14, may bring an additional aspect studies have impact diagnosis most likely also therapy cancer patients.

Language: Английский

Citations

0
Roles of anoikis in hepatocellular carcinoma therapy and the assessment of anoikis-regulatory molecules as therapeutic targets DOI
Hongyu Wang, Ya‐Wen Yang, Gan Zhang

et al.

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

Published: April 4, 2025

Language: Английский

Citations

0