Tumstatin - non-collagenous (NC1) domain of the alpha 3 chain of
type IV collagen - is a potent inhibitor of
tumor angiogenesis. Successful
tumor inhibition has been reported in
glioma, bronchopulmonary
cancer and
melanoma experimental model. In this study, the effects of
tumstatin, in vitro and in vivo, were investigated in an
oral cancer model. Recombinant human
tumstatin proteins were obtained by the transformation of Tn 5B1-4 cells, transfected with a plasmid containing
tumstatin cDNA using the lipofection method, as previously described.
Tumstatin inhibited the proliferation of human umbilical vascular endothelial cells in a dose dependent manner in a proliferation assay. For the in vivo analysis, we established an orthotopic
oral squamous cell carcinoma (AT-84 cells) animal (C3H/He) model. In this animal model, the in vivo inhibitory effects of
tumstatin on the
tumor growth and on the
metastasis of
tumors were demonstrated. However, the
tumors did not show complete remission. Immunostaining of the
tumor microvessels (CD-31/PECAM) revealed that the density of
tumor microvessels was significantly decreased in the
tumstatin treated primary
tumors. The results demonstrated that
tumstatin delayed the
tumor growth and the
metastasis of
oral squamous cell carcinomas. However,
tumstatin alone failed to achieve
tumor regression. Therefore,
tumstatin might have an adjuvant role in the treatment of
oral cancers, in combination with the conventional
therapy.