Development of diffuse invasive (grade 4D) human oral squamous cell carcinoma model in severe combined...

Among oral squamous cell carcinomas (OSCCs), the diffuse invasive (grade 4D) tumour exhibits the highest degree of malignancy. The TSU cell line, which has been established from a grade 4D OSCC, has not been successfully grown even in immuno-suppressed hosts. Here, invasive cells were selected by the repeated inoculation of TSU cells with Matrigel and gelatin sponge into the subcutaneous tissue of nude mice. The selected cells formed oral tumours temporarily in nude mice and produced lethal tumourgenicity in severe combined immunodeficiency (SCID) mice without the addition of other materials. The microangioarchitecture of the tumours in SCID mice showed neovascularization and the formation of a vascular network. An immunohistochemical study demonstrated that the expressions of vascular endothelial growth factor and matrix metalloproteinase-2 were strong, whereas desmoglein-1 and type-IV collagen were absent. These findings suggested that the loss of intercellular junctions and dissolution of basement membranes may underlie the pathogenesis of diffuse invasive growth in grade 4D tumours.