We used the model to establish the ability of the ASPH inhibitor MO-I-1151 to inhibit the invasion of HNSCC tumor cells into Matrigel, and we showed an additive inhibitory effect of its combination with a recently described heparan 6-O-endosulfatase (SULF2) inhibitor, HfFucCS. Here, SULF2 is linked to head and neck squamous cell carcinoma.