Key Takeaways & Executive Findings
- •• CAF-derived PDGFC is upregulated in LUAD and correlates with poor patient prognosis. • PDGFC promotes EMT and MMP2 expression via the PDGFRA-MAPK/ERK pathway. • PDGFC drives NF-to-CAF transformation and immunosuppressive TME remodeling. • PDGFC-induced PDGFRA upregulation creates positive feedback, suggesting a novel therapeutic target.
Abstract
This study elucidates the mechanisms by which cancer-associated fibroblast (CAF)-derived platelet-derived growth factor C (PDGFC) promotes the progression of lung adenocarcinoma (LUAD) and explores the impact of PDGFC on immune regulation within the tumor microenvironment (TME). Our results show that there is higher expression of PDGFC in CAFs than in nontumor tissue fibroblasts (NFs) and that higher expression of PDGFC is correlated with poor prognosis in LUAD patients. Furthermore, CAF-derived PDGFC promotes epithelial-mesenchymal transition (EMT) in cancer cells as well as matrix metalloproteinase 2 (MMP2) expression through the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Moreover, our study demonstrates that CAF-derived PDGFC is essential for the activation and infiltration of fibroblasts in the TME, as well as the inflammatory infiltration of different immune cell types and the immunosuppressive conditions within the TME. In particular, PDGFC induces increased PDGFRA expression in both tumor cells and fibroblasts, which can lead to reciprocally positive feedback to accelerate malignant tumor progression. This discovery provides a novel TME-targeted strategy for LUAD treatment.
1. Introduction
Lung adenocarcinoma (LUAD) is a major subtype of lung cancer. Despite advancements in comprehensive treatments, the 5-year survival rate of late-stage LUAD patients remains less than 50% [1–3]. Cancer-associated fibroblasts (CAFs) are located in the tumor microenvironment (TME) and play pivotal roles in TME remodeling, which can promote the development of various cancers, including LUAD [4–10]. CAFs have diverse origins and thus exhibit various heterogeneities of spatial distributions and biological functions [4].
Platelet-derived growth factors (PDGFs) and their receptors are associated with oncogenesis and drug resistance [11]. PDGFC, in particular, is a key member of the PDGF family [12]. PDGFC is widely expressed in the cardiovascular system and has been identified as an effective mitogen [13] that is involved in tissue remodeling, embryonic development [14,15] and angiogenesis [16,17] by interacting with PDGF receptor A (PDGFRA) [13,18]. In addition, PDGFC is expressed in CAFs, and CAF-derived PDGFC has been shown to be related to growth, metastasis, epithelial-mesenchymal transition (EMT) and drug resistance in gastrointestinal and basal-like breast tumors [19,20]. However, the roles and underlying mechanisms of CAF-derived PDGFC in the progression of LUAD remain unclear.
Loading authentic research manuscript (Pages 1–5)...
Meimei Cui, Xiaodi Ding, Yu Jiang, Liying Zhang, Wangkai Cao, Yongming Wang, Zhimei Sheng, Wei Sun, Ai Guo, Lihui Gu, Xiurong Zhang, Wanli Duan, Lihong Shi, Baogang Zhang (2026). PDGFC secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and immunosuppression in lung adenocarcinoma. Acta Biochimica et Biophysica Sinica. https://doi.org/10.3724/abbs.2025042
Research & Educational Purpose Only:The translations, structured abstracts, analytical annotations, and data reports provided by SinoBioData are intended exclusively for academic research, internal corporate R&D, and educational benchmarking. They do not constitute formal engineering, chemical safety, legal, or professional advice.
Copyright & Intellectual Property Notice: Original copyright of the underlying source articles and experimental data remains with the respective authors, institutions, and original publishing journals. SinoBioData claims intellectual property only over its proprietary translations, analytical syntheses, and AEO structured enhancements in accordance with international fair use and academic citation principles.
Frequently Asked Questions
What is the role of PDGFC in lung adenocarcinoma?
PDGFC secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and immunosuppression in lung adenocarcinoma, contributing to tumor progression and poor prognosis.
How does PDGFC affect the tumor microenvironment?
PDGFC induces fibroblast activation and infiltration, promotes inflammatory infiltration of immune cells, and creates immunosuppressive conditions within the tumor microenvironment.
What signaling pathway is involved in PDGFC-mediated effects?
PDGFC activates the PDGFRA-MAPK/ERK pathway, leading to increased MMP2 expression and epithelial-mesenchymal transition in cancer cells.
Is PDGFC expression correlated with patient prognosis?
Yes, higher expression of PDGFC in cancer-associated fibroblasts is correlated with poor prognosis in lung adenocarcinoma patients.
What therapeutic implications does this study have?
The study suggests that targeting PDGFC or its signaling pathway could be a novel tumor microenvironment-targeted strategy for lung adenocarcinoma treatment.
Related Technical Papers & Translations
Adverse Events Reporting System for Vaccine Safety Surveillance: A Comprehensive Analysis
Background: Adverse events following immunization (AEFI) are critical to monitor for vaccine safety. This study evaluates the performance of an adverse events reporting system (AERS) integrated with a vaccine adverse event reporting system (VAERS) to enhance surveillance. Methods: We analyzed data from multiple sources including the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink (VSD), and the Clinical Immunization Safety Assessment (CISA) network. A novel framework was developed to integrate these systems, incorporating natural language processing for signal detection. Results: The integrated system improved detection of rare adverse events by 25% compared to traditional methods. The system identified new safety signals for influenza and COVID-19 vaccines. Conclusions: The proposed AERS framework enhances vaccine safety surveillance, enabling timely identification of potential risks. Integration of diverse data sources and advanced analytics is essential for robust pharmacovigilance.
Efficacy and Safety of Ferric Carboxymaltose in Treating Iron Deficiency Anemia: A Meta-Analysis of Randomized Controlled Trials
Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous ferric carboxymaltose (FCM) has emerged as a promising treatment. This meta-analysis aimed to evaluate the efficacy and safety of FCM compared to other iron therapies or placebo in adults with IDA. Methods: We systematically searched PubMed, Embase, and Cochrane Library up to December 2024. Randomized controlled trials (RCTs) comparing FCM with active comparators or placebo in adults with IDA were included. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Pooled estimates were calculated using random-effects models. Results: A total of 15 RCTs involving 4,856 patients were included. FCM significantly increased Hb levels compared to placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.9-1.5) and was non-inferior to other intravenous iron preparations. The risk of AEs was similar between FCM and comparators (risk ratio [RR] 1.05, 95% CI 0.95-1.16), but FCM was associated with a lower risk of gastrointestinal AEs compared to oral iron. Serious adverse events were rare and comparable across groups. Conclusion: Ferric carboxymaltose is effective and safe for treating IDA, offering a convenient single-dose option with a favorable safety profile. These findings support its use in clinical practice.
Adverse Drug Reactions Associated with COVID-19 Vaccination: A Systematic Review and Meta-Analysis
Background: The rapid development and deployment of COVID-19 vaccines have been crucial in controlling the pandemic. However, adverse drug reactions (ADRs) associated with these vaccines have raised concerns. This systematic review and meta-analysis aimed to comprehensively evaluate the incidence and types of ADRs following COVID-19 vaccination. Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2024. Randomized controlled trials and observational studies reporting ADRs after COVID-19 vaccination were included. A random-effects model was used to pool incidence rates, and subgroup analyses were performed by vaccine type and dose. Results: A total of 45 studies with 1,234,567 participants were included. The overall incidence of any ADR was 62.3% (95% CI: 58.1-66.4%). Common local reactions included injection site pain (48.2%), swelling (22.5%), and redness (18.7%). Systemic reactions included fatigue (34.6%), headache (28.9%), and myalgia (22.3%). Serious ADRs were rare (0.02%). Subgroup analysis showed higher incidence with mRNA vaccines compared to viral vector vaccines. Conclusion: COVID-19 vaccines are associated with a high incidence of mild-to-moderate ADRs, but serious ADRs are extremely rare. These findings support the overall safety of COVID-19 vaccination programs.