Expression of the complement regulatory proteins decay accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and CD59 in the normal human uterine cervix and in premalignant and malignant cervical disease.
The membrane-bound complement regulators decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46), and CD59 are broadly expressed proteins that act together to protect host tissues from autologous complement. Comparison of expression profiles of these proteins between normal and pathological tissues could reveal a mechanism by which tumor cells evade complement-mediated killing. Expression of the regulators was therefore examined in the normal human uterine cervix, in cervical intraepithelial neoplasia (CIN; n = 23), and in cervical squamous carcinomas (n = 6). DAF and MCP were reciprocally expressed in normal ectocervical epithelium. MCP was confined predominantly to the basal and parabasal layers with more extensive expression in metaplastic squamous epithelium. An apparent expansion in MCP expression was observed in more severe premalignant lesions whereas cervical carcinoma were uniformly MCP positive. By contrast, DAF expression appeared unaltered in premalignant lesions and variable in carcinomas. However, increased DAF was observed in stromal cells directly adjacent to infiltrating tumor cells. A low molecular weight DAF product was detected in tumors, and preliminary evidence suggests this may be derived from stromal cells. Overall, changes in expression of C3 convertase regulators in both the stromal and epithelial compartments may be important for evasion of immune surveillance in cervical cancer.
Simpson
K L
KL
Department of Clinical Medicine, University of Bristol, St. Michael's Hospital, United Kingdom.
Jones
A
A
Norman
S
S
Holmes
C H
CH
D015703:Antigens, CD / Q000378:metabolism*; D018958:CD55 Antigens / Q000378:metabolism*; D018957:CD59 Antigens / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism*; D011247:Pregnancy; D012016:Reference Values; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins