EFEMP2 upregulates PD-L1 expression via EGFR/ERK1/2/c-Jun signaling to promote the invasion of ovarian cancer cells

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: July 7, 2023

Fibulin-like extracellular matrix protein 2 (EFEMP2) has been reported to be related the progression of various cancers. We have previously that EFEMP2 was highly expressed in ovarian cancer and strongly associated with poor prognosis patients. This study intends further explore its interacting proteins possible downstream signaling pathways.The expression detected by RT-qPCR, ICC western blot 4 kinds cells different migration invasion ability. Cell models strong or weak were constructed lentivirus transfection. The effects down-regulation up-regulation on biological behavior studied through in-vitro in-vivo functional tests. phosphorylation pathway profiling array KEGG database analyses identified EGFR/ERK1/2/c-Jun programmed death-1 (PD-L1) enrichment. Additionally, interaction between EGFR immunoprecipitation.EFEMP2 positively correlated ability cells, inhibited migrative, invasive cloning capacity vitro suppressed tumor proliferation intraperitoneal diffusion vivo, while did opposite. Moreover, could bind induce PD-L1 regulation cancer, which caused activation signaling. Similar EFEMP2, also aggressive had promote metastasis both upregulation partly activation. Afatinib combined trametinib an obvious effect inhibiting especially group low overexpression reverse this phenomenon.EFEMP2 activate ERK1/2/c-Jun regulate expression, furthermore extremely essential for dissemination vivo. Targeted therapy against source gene is our future research direction, may better inhibit cells.

Language: Английский

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A novel therapeutic approach targeting PD-L1 in HNSCC and bone marrow-derived mesenchymal stem cells hampers pro-metastatic features in vitro: perspectives for blocking tumor-stroma communication and signaling

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 10, 2025

Current conventional treatment regimens for head and neck squamous cell carcinoma (HNSCC), are poorly effective because of the emergence resistance mechanisms. Many studies have reported how tumor microenvironment influences response to immune checkpoint inhibitors targeting PD-1/PD-L1. It has been that overexpression PD-L1 correlates with is involved in cancer progression by promoting epithelial-to-mesenchymal-transition (EMT) program, stemness invasiveness through AKT MAPK pathways. In this study, we investigated bone marrow mesenchymal stem cells (BM-MSCs) recruited educated HNSCC able promote invasion EMT program. addition, analyzed crosstalk between stromal can affect expression levels. context, developed characterized a novel anti-PD-L1 recombinant Fab (rFab') tested its ability potentiate effect cisplatin. BM-MSCs co-cultures, migration were performed using Boyden chambers. The treatments on viability growth MTT clonogenic assay, respectively. rFab' was prepared E. Coli binding FACS analysis fluorescence microscopy. PD-L1, p-AKT, p-ERK, N-cadherin β-catenin levels western blotting. induced migrate, invade trans-differentiate associated fibroblasts (CAFs) as demonstrated increased α-SMA FAP-α. contributed increasing When co-cultured level enhanced both indicating reciprocal support favoring aggressiveness. Tumor reduced their viability, growth, blunted underlying signaling antitumor cisplatin cells. aggressiveness via PD-L1. A reduces proliferation, potentiates suggesting potential be conjugated drugs immuno-cytotoxic therapy.

Language: Английский

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Spatial interaction mapping of PD-1/PD-L1 in head and neck cancer reveals the role of macrophage-tumour barriers associated with immunotherapy response

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 12, 2025

Abstract Background Mucosal head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage, where the prognosis poor due to high rates of recurrence metastasis. With approximately one million new cases projected in 2024, worldwide mortality HNSCC estimated reach 50% detected same year. Patients with early-stage tumours showed a 50–60% five-year survival rate US. Immune checkpoint inhibitors (ICIs) have shown promising results prolonging subset patients recurrent or metastatic disease. However, challenges remain, particularly limited efficacy PD-1/PD-L1 blockade therapies. PD-L1 protein expression has been be its predictive power for ICI Emerging evidence shows that intricate characterisation tumour microenvironment (TME) fundamental understand interacting cells. This study aims bridge gap understanding tumor by identifying distinct spatial patterns interactions their association immunotherapy responses (HNSCC). Methods In this study, we sought apply more nuanced approach cellular mapping across whole-slide tissue samples collected prior therapy. We used combination proteomics (Akoya Biosciences) situ proximity ligation assay (isPLA, Navinci Diagnostics) visualise types neighbourhoods within TME. Results Our findings indicate existence isPLA + between macrophages/CD3 T cell-enriched cells tumour-stroma boundaries ICI-resistant tumours. The presence these dense macrophage-tumour layers, which are either absent dispersed responders, indicates barrier may restrict immune infiltration promote escape mechanisms. contrast, responders had abundant B aggregates, predominantly around edges linked enhanced therapy better clinical outcomes. Conclusion highlights utility detecting tumour-immune TME, offering interaction metrics stratifying optimising strategies.

Language: Английский

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Role of liposomes in chemoimmunotherapy of Breast cancer

Journal of drug targeting, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 43

Published: Feb. 19, 2025

In the dynamic arena of cancer therapeutics, chemoimmunotherapy has shown tremendous promise, especially for aggressive forms breast like triple-negative (TNBC). This review delves into significant role liposomes in enhancing effectiveness by leveraging cancer-specific mechanisms such as induction immunogenic cell death (ICD), reprogramming tumor microenvironment (TME), and enabling sequential drug release. We examine innovative dual-targeting that capitalize on heterogeneity, well pH-sensitive formulations offer improved control over delivery. Unlike prior analyses, this directly links advancements preclinical research-such PAMAM dendrimer-based nanoplatforms RGD-decorated liposomes-to clinical trial results, highlighting their potential to revolutionize TNBC treatment strategies. Additionally, we address ongoing challenges related scalability, toxicity, regulatory compliance, propose future directions personalized, immune-focused nanomedicine. work not only synthesizes latest research but also offers a framework translating liposomal from laboratory practice.

Language: Английский

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Exploring Immune Checkpoint Inhibitors: Focus on PD-1/PD-L1 Axis and Beyond

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155864 - 155864

Published: March 1, 2025

Language: Английский

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