NAB 2-Expressing Cancer-Associated Fibroblast Promotes HNSCC Progression

Cancer-associated fibroblast (CAF)-specific proteins serve as both prognostic biomarkers and targets for anticancer drugs. In this study, we investigated the role of NGFI-A-binding protein (NAB)2 derived from CAFs in the progression of head and neck squamous cell carcinoma (HNSCC). Patient-derived HNSCC and paired metastatic lymph node tissues were examined for NAB2 expression by immunohistochemistry. Primary CAF cultures were established from HNSCC patient tissue, with paired non-tumor fibroblasts (NTFs) serving as a control. CAF or NTF was used to evaluate the effect of NAB2 on HNSCC progression using FaDu cell spheroids and an in vivo mouse xenograft model. NAB2 was detected in interstitial CAFs in primary and metastatic lymph node tissues of HNSCC patients. NAB2 mRNA and protein levels were higher in CAFs as compared to paired NTFs. Conditioned medium (CM) of NAB2-overexpressing CAFs increased the invasion of FaDu spheroids in the Matrigel invasion assay as compared to CM of NTF. Co-injection of NAB2-overexpressing CAFs with FaDu spheroids into mice enhanced the growth of tumors. These data suggest that NAB2-overexpressing CAFs promotes HNSCC progression and is a potential therapeutic target for preventing HNSCC metastasis.