Invasion of extracellular matrix by cultured colon cancer cells: dependence on urokinase receptor display.
Several urokinase-expressing tumor cells display surface receptors that avidly bind the plasminogen activator. The present study was undertaken to determine the importance of receptor bound urokinase in promoting the invasive phenotype by cultured colon cancer cells. An HCT 116 cell line that elaborates urokinase and displays 11 x 10(4) receptors per cell, 57% of which are tagged with endogenous plasminogen activator, invaded extracellular matrix (Matrigel) in a plasminogen dependent manner. Matrigel invasion was contingent on plasmin production mediated by urokinase, since epsilon-aminocaproic acid diminished the invasive capacity of the HCT 116 cells by 75%. A specific urokinase receptor peptide-antagonist reduced cell invasion in a dose dependent manner with a maximum effect (78% reduction in tumor cell infiltration) being achieved with a 10(-4) M concentration. These results did not reflect a non-specific "shut down" of urokinase expression by the receptor antagonist insofar as steady state urokinase transcript levels were unchanged compared with untreated controls. In addition, LH-RH, a control peptide, failed to suppress Matrigel invasion by HCT 116 cells. The CBS and FET colon cancer cell lines, which secrete amounts of urokinase similar to HCT 116 cells and display one tenth of the receptor number were found to be poorly invasive. Over a three day period, less than 0.8% of these cells invaded the Matrigel in contrast to the 6.9% seen for HCT 116 cells. These data suggest that for cultured colon cancer cells, at least, the display of receptor bound urokinase was a prerequisite for plasminogen dependent invasion.
Schlechte
W
W
Bristol-Baylor Laboratory, Baylor College of Medicine, Houston, TX 77030.
Brattain
M
M
Boyd
D
D
D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology; D046508:Culture Techniques / Q000295:instrumentation / Q000379:methods; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D010958:Plasminogen / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000502:physiology
C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator