Potenzielle Rolle der thrombozytenvermittelten epithelial-mesenchymalen Transition beim Plattenepithelkarzinom des Kopf-Hals-Bereichs

Introduction

Epithelial-mesenchymal transition (EMT) is crucial for cancer cell migration and metastasis and is driven by a multitude of stimulators, such as growth factors, cytokines, and exosomes. Tumor-educated platelets (TEPs) are rich in EMT-promoting signaling molecules, which may further enhance metastasis in various cancers, including head and neck squamous cell carcinoma (HNSCC). Therefore, we hypothesize that TEPs have the potential to interfere with EMT.

Materials and methods

The human oral squamous cell carcinoma cell line SAS was co-cultured with platelets (PLTs) isolated from healthy (HPs) and tumor-bearing (TEPs) donors. EMT-related surface marker expression on SAS cells was quantified by flow cytometry at 3, 6, and 9 days post-co-culture. The impact of HP-derived exosomes (HPEX) and TEP-derived exosomes (TEPEX), known as major mediators of PLT communication with other cells, was evaluated using a transwell assay and the exosomal signature of HPEX and TEPEX was determined by proteomic analysis.

Results

The epithelial phenotype of SAS cells was confirmed. Upon exposure to HPs and TEPs, a shift towards a mesenchymal phenotype was observed. A comparative analysis conducted over the indicated incubation period revealed distinct EMT induction kinetic patterns between HPs and TEPs. Transwell assays demonstrated that factors secreted by HPs and TEPs, including HPEX and TEPEX, induce EMT in SAS cells even in the absence of direct cell-cell contact. Moreover, proteomic profiling revealed an enrichment of EMT-related proteins in TEPEX relative to HPEX.

Discussion

Our study provides insights into PLT-tumor cell interactions, suggesting that PLTs, particularly through TEPEX, may serve as potential target to inhibit EMT and reduce metastasis in HNSCC patients.

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