# Interventional effects of mesenchymal stem cells on epithelial–mesenchymal transition in head and neck squamous cell carcinoma and underlying mechanisms: a systematic review and meta-analysis of in vitro studies

**Authors:** Youhu Wang, Yanli Liu, Wanxian Du, Jing Xue, Jianhua Ruan, Juan Yu, Bin Ma, Xun Li

PMC · DOI: 10.3389/fimmu.2025.1705852 · Frontiers in Immunology · 2026-01-07

## TL;DR

This study reviews how mesenchymal stem cells may promote cancer progression by influencing a process called epithelial-mesenchymal transition in head and neck cancers.

## Contribution

A systematic review and meta-analysis of in vitro studies on mesenchymal stem cells and epithelial-mesenchymal transition in head and neck squamous cell carcinoma.

## Key findings

- MSCs may reduce epithelial markers and increase mesenchymal markers in cancer cells.
- MSCs could promote EMT through multiple signaling pathways like NF-κB and TGF-β/Smad.
- More high-quality studies are needed to confirm these findings and their therapeutic potential.

## Abstract

MSCs are an important component of the TME and play a key role in tumor progression. Based on existing in vitro studies, this research aims to investigate the role of mesenchymal stem cells in the EMT of HNSCC and its related mechanisms.

According to the PRISMA guidelines, we systematically searched PubMed, Embase, and Web of Science databases for relevant in vitro studies up to May 6, 2024. Two trained researchers independently performed literature screening, data extraction, and quality assessment, with cross-checking of results. Any disagreements were resolved through discussion or by consulting a third party. Meta-analysis was conducted using Stata 17 software.

A total of 8 in vitro studies were included, involving OSCC, NPC, and TSCC. The meta-analysis results indicate that MSC intervention may be associated with a reduction in the expression of epithelial markers and an increase in mesenchymal markers and related transcription factors in cancer cells, implying a potential role for MSCs in promoting EMT in vitro. Furthermore, a preliminary review of the underlying molecular mechanisms suggests that this process may involve the potential regulation of multiple signaling pathways, including NF-κB, PI3K/Akt/mTOR, IL-6R/JAK/STAT3, CXCL8/CXCR2, TGF-β/Smad, and FGF19-FGFR4.

The existing in vitro evidence suggests that mesenchymal stem cells may exhibit a potential to promote EMT in HNSCC, potentially regulating tumor progression through multiple signaling pathway networks and providing new potential targets for future therapies targeting the TME. However, more high-quality, standardized in vivo and in vitro studies are needed to further validate the related mechanisms and therapeutic potential.

## Linked entities

- **Proteins:** NFKB1 (nuclear factor kappa B subunit 1)
- **Diseases:** head and neck squamous cell carcinoma (MONDO:0010150), HNSCC (MONDO:0010150), NPC (MONDO:0011775)

## Full-text entities

- **Genes:** STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, FGFR4 (fibroblast growth factor receptor 4) [NCBI Gene 2264] {aka CD334, JTK2, TKF}, FGF19 (fibroblast growth factor 19) [NCBI Gene 9965], IL6R (interleukin 6 receptor) [NCBI Gene 3570] {aka CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA}, CXCR2 (C-X-C motif chemokine receptor 2) [NCBI Gene 3579] {aka CD182, CDw128b, CMKAR2, IL8R2, IL8RA, IL8RB}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}
- **Diseases:** NPC (MESH:D052556), HNSCC (MESH:D000077195), cancer (MESH:D009369)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12862828/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12862828/full.md

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Source: https://tomesphere.com/paper/PMC12862828