Inhibition of decay-accelerating factor (CD55) attenuates prostate cancer growth and survival in vivo.
Decay-accelerating factor (CD55) is a member of membrane-bound complement-regulatory proteins. CD55 expression correlates with poor survival in patients with colorectal cancer and has been implicated in the survival and tumorigenesis of blood-borne malignancies. Histologic analysis of clinical specimens from patients with advanced prostate cancer revealed an increase in CD55 expression in prostate tumor epithelial cells. CD55 was shown to be functionally active and to inhibit complement-mediated lysis in PC-3 and DU145 cells. The percentage of lysis was correlative with the CD55 expression profile observed in these prostate cancer cell lines. These data suggest that CD55 is an important regulator of prostate cancer cell survival. As a result, we have hypothesized that CD55 expression on prostate cancer cells promotes cell survival and contributes to the metastatic potential of prostate cancer cells. To determine the role of CD55 in prostate cancer tumorigenesis and metastasis, we generated PC-3(Luc) prostate cancer cells with CD55 siRNA-targeted disruption. We found that PC-3(Luc)/CD55 siRNA constructs in SCID mice resulted in a significant attenuation of overall tumor burden. Further investigation into the mechanisms of CD55-mediated tumor cell/microenvironment interaction is necessary to understand the role of CD55 in tumor cell survival and metastatic lesion formation.
Loberg
Robert D
RD
Department of Urology, University of Michigan Urology Center, Ann Arbor, MI, USA. rloberg@umich.edu
Day
LaShon L
LL
Dunn
Rodney
R
Kalikin
Linda M
LM
Pienta
Kenneth J
KJ
D000818:Animals; D018958:CD55 Antigens / Q000096:biosynthesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D016896:Treatment Outcome
D018958:CD55 Antigens; D006023:Glycoproteins; D034741:RNA, Small Interfering