Utilizing a GnRH-based chimeric protein for the detection of adenocarcinoma.
Since early diagnosis of many types of cancer greatly improves the chances for successful treatment, high-quality methods for cancer detection are necessary. Our laboratory develops chimeric proteins for targeted therapy, such as gonadotropin releasing hormone (GnRH)-based chimeric proteins for the targeted therapy of adenocarcinomas in humans. For chimeric proteins to cause specific cell death, they must first recognize specific receptors/binding sites expressed on the surface of target cells. Thus, we examined whether we could exploit these binding sites not only as targets for the killing of specific cells but also as a diagnostic marker for identifying adenocarcinomas, using the same chimeric proteins. In this report, we show that one such GnRH-based chimeric protein, GnRH-Caspase3, can indeed serve as a diagnostic tool. GnRH-Caspase3 was able to specifically bind adenocarcinoma cells, as measured by FACS analysis and demonstrated with the aid of confocal microscopy and specific antibodies. Moreover, we found a correlation between cell sensitivity to treatment and the binding level of the chimeric protein to the cells. Hence, we suggest that in addition to their therapeutic potential, GnRH-based chimeric proteins can be used as a diagnostic tool for the detection of adenocarcinomas.
Lichtenstein
Michal
M
Department of Cellular Biochemistry and Human Genetics, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ben-Yehudah
Ahmi
A
Belostotsky
Ruth
R
Eaveri
Ronen
R
Sabag
Ofra
O
Grodzovski
Inna
I
Lorberboum-Galski
Haya
H
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D001665:Binding Sites; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000378:metabolism; D012680:Sensitivity and Specificity
D011993:Recombinant Fusion Proteins; D007987:Gonadotropin-Releasing Hormone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases