Interleukin-13 receptors on human prostate carcinoma cell lines represent a novel target for a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin.
We have discovered a new cell surface protein in the form of interleukin-13 receptor on several solid tumor cells, including human renal cell carcinoma cells (Obiri et al., 1995; Debinski et al., 1995). This study reports that human prostate cancer cell lines also express high affinity IL-13 receptors (Kd = 159 pM). These receptors are functional because IL-13 surprisingly increased proliferation of all three prostate cancer cell lines studied as determined by thymidine uptake and clonogenic assays. IL-13 receptors on prostate cancer cell lines were targeted using a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (PE38QQR). This molecule, termed IL13-PE38QQR, has been found cytotoxic to all three prostate cancer cell lines as determined by the inhibition of protein synthesis. The IC50 ranged between 1 nmol/l, to 15 nmol/l. These data were confirmed by clonogenic assays in which IL13-PE38QQR almost completely inhibited colony formation at 10 nmol/l. IL13-PE38QQR was not cytotoxic to cells that express little or no IL-13R. Heat inactivated IL13-PE38QQR was not cytotoxic to prostate cancer cells indicating specificity. IL13-PE38QQR was also cytotoxic to colonies when they were allowed to form first for several days before the addition of toxins. Our data suggest that additional studies should be performed to target IL-13 receptor bearing prostate cancer.
Maini
A
A
Department of Urology, State University of New York at Syracuse, USA.
Hillman
G
G
Haas
G P
GP
Wang
C Y
CY
Montecillo
E
E
Hamzavi
F
F
Pontes
J E
JE
Leland
P
P
Pastan
I
I
Debinski
W
W
Puri
R K
RK
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D002455:Cell Division; D003601:Cytotoxicity Tests, Immunologic; D005098:Exotoxins / Q000235:genetics / Q000276:immunology; D006801:Humans; D018793:Interleukin-13; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018123:Receptors, Interleukin / Q000032:analysis / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D018793:Interleukin-13; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A