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

Area of Science:

• Oncology
• Cancer Biology
• Fibroblast Research

Background:

• Cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression across various cancers, including head and neck squamous cell carcinoma (HNSCC).
• The extracellular sulfatase SULF1 is identified as a significant stromal factor highly expressed in CAFs, correlating with unfavorable patient prognosis in HNSCC.

Purpose of the Study:

• To investigate the functional role of SULF1, specifically within CAFs, in modulating HNSCC progression.
• To assess the therapeutic potential of targeting CAF-derived SULF1 in HNSCC.

Main Methods:

• Utilized CRISPR/Cas9 gene editing to create SULF1-knockout (KO) primary HNSCC CAFs.
• Performed in vitro assays to evaluate fibroblast proliferation, cancer cell migration, and invasion.
• Employed two-photon microscopy for 3D spheroid co-culture analysis.
• Conducted proteomic analysis to confirm SULF1 absence and assess SULF2 compensation.

Main Results:

• SULF1 deficiency in CAFs led to reduced fibroblast proliferation.
• Loss of SULF1 in CAFs significantly impaired HNSCC cell migration and invasion in vitro.
• 3D co-cultures showed that SULF1-deficient CAFs failed to support cancer cell invasiveness, altering spheroid morphology and reducing invasive projections.
• Proteomic analysis confirmed SULF1 knockout and indicated no compensatory role for tumor cell-expressed SULF2.

Conclusions:

• CAF-derived SULF1 is a critical regulator of tumor invasion in HNSCC.
• SULF1 emerges as a potential therapeutic target for HNSCC treatment.