title: Human carcinomas variably express the complement inhibitory proteins CD46 (membrane cofactor protein), CD55 (decay-accelerating factor), and CD59 (protectin).
abstract: Normal human tissues express membrane-associated complement inhibitory proteins that protect these tissues from damage by autologous complement. To determine whether neoplasms also express these proteins, we examined the distribution of the complement inhibitors decay-accelerating factor (DAF), CD59 (protectin), and membrane cofactor protein in frozen samples of human breast, colon, kidney, and lung carcinomas and in adjacent non-neoplastic tissues, using immunohistochemistry. All samples were also studied for deposition of C3 fragments and activated C5b-9. Differences between normal tissues and the corresponding neoplasms were often observed, with loss or gain of expression of one or more inhibitors. Ductal carcinomas of the breast showed the most variation in phenotype; some tumors expressed only one inhibitor while others expressed different combinations of two or three inhibitors. Colon carcinomas, by contrast, stained intensely for all inhibitors. Renal cell carcinomas had weak to moderate expression of one to three inhibitors, generally DAF and CD59, whereas non-small cell carcinomas of the lung usually expressed CD59 and membrane cofactor protein with variable DAF immunoreactivity. The two small cell carcinomas of the lung showed little or no staining for any inhibitor. Activated C5b-9 deposition was seen adjacent to tumor nests in a minority of carcinomas and showed no correlation with complement inhibitor expression. C3 fragment deposition was minimal. Our results demonstrate that most carcinomas, with the exception of small cell carcinomas of the lung, do express one or more complement inhibitors at a level likely to inhibit complement-mediated cellular damage. Unexpectedly, large quantities of DAF and CD59 were often observed in tumor stroma, with only limited deposition in normal connective tissue. This suggests that carcinomas may supplement the activity of membrane-associated complement inhibitors by release of soluble forms of DAF and CD59 into the surrounding extracellular matrix.
authors.affiliation: Pathology and Laboratory Medicine Service, Minneapolis Veterans Affairs Medical Center, MN, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Niehans
authors.forename: D L
authors.initials: DL
authors.lastname: Cherwitz
authors.forename: N A
authors.initials: NA
authors.lastname: Staley
authors.forename: D J
authors.initials: DJ
authors.lastname: Knapp
authors.forename: A P
authors.initials: AP
authors.lastname: Dalmasso
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000737:chemistry; D018958:CD55 Antigens / Q000032:analysis*; D018957:CD59 Antigens / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry*; D003106:Colon / Q000737:chemistry; D003110:Colonic Neoplasms / Q000737:chemistry; D003176:Complement C3 / Q000032:analysis; D003169:Complement Inactivator Proteins / Q000032:analysis*; D015938:Complement Membrane Attack Complex / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry; D007680:Kidney Neoplasms / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000737:chemistry; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis*
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003176:Complement C3; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins