Abstract

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.

Highlights

  • Cancer-associated fibroblasts (CAFs) constitute a sub-population of cells in the cancer stroma with a myofibroblast-like phenotype [1,2] that contribute to tumor progression and are, prognostic biomarkers [3]

  • NAB2 Is Expressed in Cancer-Associated Fibroblasts (CAFs) of Head and Neck Squamous Cell Carcinoma (HNSCC) Patient Tumor Tissues

  • NAB2 was highly expressed in interstitial CAFs of primary tumor (Figure 1B) and metastatic (Figure 1F) lymph node as compared to their cancer cells

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Summary

Introduction

Cancer-associated fibroblasts (CAFs) constitute a sub-population of cells in the cancer stroma with a myofibroblast-like phenotype [1,2] that contribute to tumor progression and are, prognostic biomarkers [3]. CAFs secrete growth factors and chemokines that alter the extracellular matrix (ECM) and oncogenic signals, thereby increasing the proliferation and invasion of cancer cells [4]; they have been shown to promote cancer progression in vivo when co-injected with tumor cells or are recruited to the tumor site [5,6]. Irradiated fibroblasts or the medium in which they are grown can enhance the tumorigenicity of breast cancer grafts, which may be a transient effect of CAF-secreted factors [7].

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