Role of urokinase plasminogen activator receptor in thrombospondin 1-mediated tumor cell invasion.

We previously showed that thrombospondin 1 (TSP-1) upregulates the plasminogen/plasmin system and promotes breast tumor cell invasion. Preliminary data from our laboratory using neutralizing antibodies suggested that the upregulation in breast tumor cell invasion seen in response to TSP-1 involved the urokinase plasminogen activator receptor (uPAR). To confirm these findings in MDA-MB-231 breast cancer cells, we developed three other strategies to study the role of uPAR in tumor cell adhesion and TSP-1-mediated tumor cell invasion: (a) enzymatic cleavage of uPAR with glycosylphosphatidylinositol-specific phospholipase C; (b) inhibition at the mRNA level with a uPAR antisense construct (cells named LKAS-MDA); (c) inhibition of plasminogen binding with the lysine analogue epsilon-aminocaproic acid. Adhesion to laminin and type I and type IV collagen with and without the addition of epsilon-aminocaproic acid was studied. Tumor cell invasion was studied in a modified Boyden chamber collagen invasion assay. Antisense uPAR inhibition decreased uPAR expression by 48-66% and cell-associated urokinase plasminogen activator (uPA) by 30-68%. Additionally, antisense uPAR inhibition induced a 68-70% reduction in uPA and plasmin activities. Antisense uPAR transfection increased tumor cell adhesion by 46-53%. A similar effect was observed in epsilon-aminocaproic acid-treated MDA-MB-231 cells. TSP-1-mediated tumor cell invasion was almost completely inhibited by either antisense uPAR inhibition or treatment with phospholipase C or epsilon-aminocaproic acid. We conclude that uPAR plays a crucial role in the regulation of tumor cell adhesion and TSP-1-mediated tumor cell invasion.

Albo D ，Berger DH ，Rothman VL ，Tuszynski GP ... -  《JOURNAL OF SURGICAL RESEARCH》

Thrombospondin-1 up-regulates tumor cell invasion through the urokinase plasminogen activator receptor in head and neck cancer cells.

Albo D ，Tuszynski GP 《JOURNAL OF SURGICAL RESEARCH》

The effect of thrombospondin-1 and TGF-beta 1 on pancreatic cancer cell invasion.

Albo D ，Berger DH ，Tuszynski GP 《JOURNAL OF SURGICAL RESEARCH》

Calcitonin inhibits invasion of breast cancer cells: involvement of urokinase-type plasminogen activator (uPA) and uPA receptor.

Han B ，Nakamura M ，Zhou G ，Ishii A ，Nakamura A ，Bai Y ，Mori I ，Kakudo K ... -  《INTERNATIONAL JOURNAL OF ONCOLOGY》

Tumour cell thrombospondin-1 regulates tumour cell adhesion and invasion through the urokinase plasminogen activator receptor.

Albo D ，Rothman VL ，Roberts DD ，Tuszynski GP ... -  《-》