Urokinase receptors in lung cancer and normal lung.
Cell membranes from ten non-small cell lung cancers and four specimens of adjacent lung tissue were assessed for the presence of urokinase type plasminogen activator (uPA) receptors. Displacement binding studies using 125I labelled urokinase showed specific binding on lung cancer and lung membrane preparations. Scatchard analysis showed that the dissociation constant of high affinity sites on tumour membranes was 2.9 x 10(-11) M/1 and on lung membranes was 2 x 10(-9) M/1. The concentration of high affinity binding sites on tumour membrane was 54 fmol/mg of membrane protein and on normal lung membrane was 170 fmol/mg protein. Two-point binding assays showed specific binding of urokinase on five of eight tumour membranes and one of three normal lung membranes. There was no correlation between the amount of urokinase bound and tumour subtype or extent of disease. Because of interactions between uPA and epidermal growth factor receptors (EGFr) in cell culture and because lung cancers express increased EGFr we studied the association of uPA receptors and EGFr. Seven tumours expressed EGFr at 6.8-67.6 fmol/mg of protein of EGFr and four normal lung membranes had EGFr at 5.2-15.6 fmol/mg protein EGFr. There was no correlation between uPA receptors and EGFr in this series. We conclude that non-small cell lung cancers carry receptors for urokinase and this provides a novel mechanism for control of local proteolysis.
Veale
D
D
Department of Respiratory Medicine, Freeman Hospital, Newcastle-upon-Tyne, England.
Needham
G
G
Harris
A L
AL
D000230:Adenocarcinoma / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D006801:Humans; D008168:Lung / Q000032:analysis* / Q000378:metabolism; D008175:Lung Neoplasms / Q000032:analysis* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D066246:ErbB Receptors; D014568:Urokinase-Type Plasminogen Activator