Cancer-associated fibroblasts in the invasive tumour front promote the metastasis of oral squamous cell carcinoma through MFAP5 upregulation

• Published in: Gene 2023-08, Vol.876, p.147504-147504, Article 147504
• Main Authors: Wang, Yujia, Wang, Ruixin, Li, Bowen, Huang, Zhuoshan, Zhao, Sufeng, Chen, Suling, Lan, Tianjun, Ren, Siqi, Wu, Fan, Tan, Jing, Li, Jinsong
• Format: Article
• Language: English
• Subjects: Cancer-Associated Fibroblasts - metabolism; Carcinoma, Squamous Cell - genetics; Cell Line, Tumor; Extracellular matrix; Fibroblasts - metabolism; Head and Neck Neoplasms - pathology; Head and neck squamous cell carcinoma; Humans; Migration; Mouth Neoplasms - genetics; Proliferation; Squamous Cell Carcinoma of Head and Neck - pathology; Tumor Microenvironment - physiology; Tumour invasion; Tumour microenvironment; Up-Regulation
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2023.147504

•Invasive tumour front played an important role in invasion and metastasis.•CAFs from the invasive front promoted tumour progression more significantly than CAFs from the superficial tumour in OSCC.•Invasive tumour front CAFs promoted the OSCC progression through MFAP5. Cancer-associated fibroblasts (CAFs) are widely involved in the development and progression of tumours. As a direct junction between tumour and normal host tissue, the invasive tumour front can remodel host tissue to generate a microenvironment more suitable for tumour invasion. However, whether CAFs derived from the invasive front (CAFs-F) have a greater ability to promote tumour invasion than CAFs derived from the superficial tumour (CAFs-S) is unclear. In this study, we characterized primary CAFs from different spatial locations of tumours. We demonstrated that CAFs-F had an increased ability to promote oral squamous cell carcinoma (OSCC) proliferation and invasion in vitro and significantly enhanced tumour growth in vivo compared to CAFs-S. Mechanistically, transcriptome profiling analysis revealed that the expression of MFAP5, encoding microfibril associated protein 5, was dramatically increased in CAFs-F compared to CAFs-S, which further confirmed that the MFAP5 protein level was elevated in head and neck squamous cell carcinoma (HNSCC) and that this increase was correlated with poor survival. Genetic ablation of MFAP5 impaired the preinvasive capabilities of CAFs-F. Together, our findings demonstrated that CAFs-F had a greater ability to promote tumour invasion than CAFs-S and that MFAP5 might be involved in this process.