Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression.
The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its blockade plays a critical role in carcinogenesis and progression in several malignancies. However, the function of Fas-FasL system in urothelial cancer (UC) has not been elucidated. We therefore investigated the expression of Fas, FasL and Decoy receptor 3 for FasL (DcR3) in UC specimens and cell lines, and examined the cytotoxic effect of an anti-Fas-activating monoclonal antibody (mAb) in vitro. Immunohistochemical examinations of Fas-related molecules were performed on 123 UC and 30 normal urothelium surgical specimens. Normal urothelium showed Fas staining in the cell membrane and cytoplasm. In UC, less frequent Fas expression was significantly associated with a higher pathological grade (P < 0.0001), a more advanced stage (P = 0.023) and poorer prognosis (P = 0.010). Fas and the absence thereof were suggested to be crucial factors with which to select patients requiring more aggressive treatment. Moreover, low-dose anti-Fas-activating mAb sensitised resistant cells to adriamycin, and this synergistic effect could be applied in the development of new treatment strategy for UC patients with multidrug-resistant tumours.
Yamana
K
K
Division of Molecular Oncology, Department of Signal Transduction Research, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata 951-8510, Japan.
Bilim
V
V
Hara
N
N
Kasahara
T
T
Itoi
T
T
Maruyama
R
R
Nishiyama
T
T
Takahashi
K
K
Tomita
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D010386:Pelvic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014516:Ureteral Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D019014:fas Receptor / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; D019014:fas Receptor; D004317:Doxorubicin