Expression of Fas in renal cell carcinoma.
We have investigated whether the Fas-mediated cell death pathway is functional in renal cell carcinoma. The expression of Fas in surgical specimens and cell lines of renal cell carcinoma was examined. Fas expression was positive in six out of 18 tumors measured by flow cytometry and was prominent in advanced tumors. Three out of the six Fas-positive tumors had already metastasized at the time of surgery. A significant correlation was found between the tumor volume and the percentage of Fas-positive cells in a tumor (r = 0.70, P = 0.0007). Fas-positive tumors were larger than Fas-negative tumors [mean tumor volume (ml) +/- SD, Fas(+), 265.6 +/- 136.8; Fas(-), 65.8 +/- 80.9, P = 0.0012]. All human renal carcinoma cell lines tested (ACHN, Caki-1, SMKT-R-2, SMKT-R-3 and SMKT-R-4) expressed Fas abundantly, as Fas-positive cells accounted for > 50% in all cell lines by flow cytometry. Treatment with anti-Fas antibody caused apoptosis in Fas-positive renal cell carcinoma cell lines. However, the effectiveness of apoptosis induction in individual cell lines was not correlated with the level of Fas expressed. These data suggest that Fas targeting may be a therapeutic option for treatment of advanced renal cell carcinoma which is refractory to either chemotherapy or irradiation.
Horie
S
S
Division of Urology, National Cancer Center Hospital, Tokyo, Japan. shorie@gan2.ncc.go.jp
Kano
M
M
Higashihara
E
E
Moriyama
N
N
Tanaka
E
E
Hirose
A
A
Kakizoe
T
T
Kawabe
K
K
D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000556:secondary; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism* / Q000502:physiology
D019014:fas Receptor