Expression of complement factor H by lung cancer cells: effects on the activation of the alternative pathway of complement.
The complement system is important in immunosurveillance against tumors. However, malignant cells are usually resistant to complement-mediated lysis. In this study, we examine the expression of factor H, an inhibitor of complement activation, and factor H-like protein 1 (FHL-1), its alternatively spliced form, in lung cancer. We also evaluate the potential effect of factor H/FHL-1 in the protection of lung cancer cells against the activation of the complement cascade. By Northern blot analysis we demonstrate a high expression of factor H and FHL-1 in most non-small cell lung cancer cell lines, although neuroendocrine pulmonary tumors (small cell lung carcinoma and carcinoid cell lines) had undetectable levels. Western blot analysis of conditioned medium showed the active secretion of factor H and FHL-1 by cells that were positive by Northern blot. Expression of factor H/FHL-1 mRNA was also shown in a series of non-small cell lung cancer biopsies by in situ hybridization. Interestingly, many cultured lung cancer cells were able to bind fluorescence-labeled factor H to their surfaces. Deposition of C3 fragments from normal human serum on H1264, a lung adenocarcinoma cell line, was more efficient when factor H/FHL-1 activity was blocked by specific antibodies. Blocking factor H/FHL-1 activity also enhanced the release of anaphylatoxin C5a and moderately increased the susceptibility of these cells to complement-mediated cytotoxicity. In summary, we demonstrate the expression of factor H and FHL-1 by some lung cancer cells and analyze the contribution of these proteins to the protection against complement activation.
Ajona
Daniel
D
Division of Oncology, Center for Applied Medical Research, Pamplona, Spain.
Castaño
Zafira
Z
Garayoa
Mercedes
M
Zudaire
Enrique
E
Pajares
Maria J
MJ
Martinez
Alfredo
A
Cuttitta
Frank
F
Montuenga
Luis M
LM
Pio
Ruben
R
D001798:Blood Proteins / Q000096:biosynthesis / Q000276:immunology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003179:Complement C3b / Q000276:immunology / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins; D015936:Complement C5a / Q000096:biosynthesis / Q000276:immunology; D017242:Complement Factor H / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism
D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D003179:Complement C3b; D015936:Complement C5a; D017242:Complement Factor H