# SULF1 in Cancer Associated Fibroblasts Promotes Invasion in Head and Neck Cancer Cell Lines

## TL;DR

This study shows that SULF1 in cancer-associated fibroblasts helps head and neck cancer cells invade, suggesting it could be a new treatment target.

## Contribution

The study identifies SULF1 in cancer-associated fibroblasts as a novel driver of tumor invasion in head and neck cancer.

## Key findings

- Loss of SULF1 in CAFs reduces fibroblast proliferation and cancer cell migration in vitro.
- SULF1-deficient CAFs fail to support cancer cell invasion in 3D spheroid cocultures.
- SULF2 does not compensate for the loss of SULF1 in these models.

## Abstract

Cancer‐associated fibroblasts (CAFs) significantly influence tumor behavior in head and neck squamous cell carcinoma (HNSCC) and other malignancies. We identified the extracellular sulfatase SULF1 as a key stromal factor highly expressed in CAFs and associated with poor prognosis.

Using CRISPR/Cas9‐edited SULF1‐knockout primary HNSCC CAFs, we demonstrate that loss of SULF1 reduces fibroblast proliferation and markedly impairs cancer cell migration and invasion in vitro. Two‐photon microscopy in 3D spheroid cocultures revealed that SULF1‐deficient CAFs fail to support invasiveness of Cal33 cells, resulting in spheroids with fewer invasive projections and altered morphology. Proteomic analysis confirmed the absence of SULF1 in the knockout cell cultures and revealed that SULF2, expressed in tumor cells, does not compensate for its loss.

These findings highlight the importance of CAF‐derived SULF1 in regulating tumor invasion and suggest that SULF1 is a promising therapeutic target in HNSCC.