The Overexpression of Fibronectin 1 Promotes Cancer Progression and Associated with M2 Macrophages Polarization in Head and Neck Squamous Cell Carcinoma Patients

Wan-Hang Zhou; Wei-Dong Du; Yan-Fei Li; Maged Ali Al-Aroomi; Cong Yan; Yao Wang; Ze-Ying Zhang; Fa-Yu Liu; Chang-Fu Sun

doi:10.2147/IJGM.S364708

The Overexpression of Fibronectin 1 Promotes Cancer Progression and Associated with M2 Macrophages Polarization in Head and Neck Squamous Cell Carcinoma Patients

Int J Gen Med. 2022 May 17:15:5027-5042. doi: 10.2147/IJGM.S364708. eCollection 2022.

Authors

Wan-Hang Zhou¹, Wei-Dong Du¹, Yan-Fei Li², Maged Ali Al-Aroomi¹, Cong Yan¹, Yao Wang¹, Ze-Ying Zhang¹, Fa-Yu Liu¹, Chang-Fu Sun¹

Affiliations

¹ Department of Oral Maxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University; Oral Diseases Laboratory of Liaoning, Shenyang, 110000, People's Republic of China.
² Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, People's Republic of China.

Abstract

Purpose: This study aimed to investigate the biological roles of fibronectin 1 (FN1) in head and neck squamous cell carcinoma (HNSCC) and its effects on macrophage M2 polarization.

Methods: We analyzed FN1 expression pattern and examined its clinical relevance in HNSCC progression by bioinformatic analysis. Small interfering RNA (siRNA) was utilized to silence FN1 in HNSCC cells. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell assay and wound healing assay were performed to reveal the effect of FN1 on malignant behaviors of HNSCC cells. Moreover, a co-culture model of macrophages and HNSCC cells was established to investigate whether FN1 induce macrophage M2 polarization. Finally, we used bioinformatic methods to explore the possible FN1-related pathways in HNSCC.

Results: FN1 is significantly overexpressed in HNSCC patients and has been obviously correlated with higher pathological stage and poor prognosis. Downregulation of FN1 suppressed the proliferation, migration and invasion of HNSCC cells, and inhibited macrophage M2 polarization in vitro. In addition, "PI3K-Akt" and "MAPK" signaling pathways may be involved in the malignant process of FN1 in HNSCC.

Conclusion: The overexpression of FN1 promotes HNSCC progression and induces macrophages M2 polarization. FN1 may serve as a promising prognostic biomarker and therapeutic target in HNSCC.

Keywords: fibronectin 1; head and neck squamous cell carcinoma; macrophages; prognosis; tumorigenesis.