Thrombospondin-1 up-regulates tumor cell invasion through the urokinase plasminogen activator receptor in head and neck cancer cells.
BACKGROUND
We have previously demonstrated that thrombospondin-1 (TSP-1) is expressed in squamous cell carcinomas of the head and neck. We have also shown that TSP-1 promotes tumor cell invasion through up-regulation of the urokinase plasminogen activator receptor (uPAR), in adenocarcinoma models. We now determined the role of TSP-1 in the regulation of uPAR expression and tumor cell invasion in squamous cell carcinoma of the head and neck cells.


METHODS
KB squamous cell carcinoma of the head and neck cells were used. The effect of TSP-1 on uPAR and its ligand, urokinase plasminogen activator (uPA), expression were determined by ELISA. The effect of TSP-1 on KB tumor cell invasion was determined in a modified Boyden chamber collagen invasion assay. To determine the role of uPAR on TSP-1-mediated KB tumor cell invasion, we used the three following different strategies: (a). blocking uPAR or its ligand, uPA, with neutralizing antibodies; (b). enzymatic cleavage of uPAR with glycosylphosphatidylinositol (GPI)-specific phospholipase C; and (c). inhibition of plasminogen binding by using epsilon-aminocaproic acid.


RESULTS
TSP-I up-regulated uPAR and uPA expression 3- and 4-fold, respectively. TSP-1 up-regulated KB tumor cell invasion 5-fold. Inhibition of uPAR blocked the TSP-1-mediated up-regulation of KB tumor cell invasion.


CONCLUSIONS
Our data support a central role for TSP-1 in the regulation of uPAR and tumor cell invasion in squamous cell carcinomas of the head and neck cells. Furthermore, uPAR seems to play a crucial role in TSP-1-mediated squamous cell carcinoma of the head and neck tumor cell invasion.
Albo
D
D
Medical College of Georgia, Department of Surgery, Section of Surgical Oncology, Augusta, Georgia, USA. dalbo@mail.mcg.edu
Tuszynski
G P
GP
D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D011956:Receptors, Cell Surface / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D019700:Thrombospondin 1 / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019700:Thrombospondin 1