Expression of Complement Factor H by Lung Cancer Cells

Abstract

The complement system is important in immunosurveillance against tumors. However, malignant cells are usually resistant to complementmediated 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.

Quantification of Fucosylated Hemopexin and Complement Factor H in Plasma of Patients with Liver Disease

“…CFH, a 140 kDa plasma glycoprotein with nine N-glycosylation sites, is a major regulator of the alternative complement pathway 39 that mediates the escape of malignant cells from complement-cytotoxicity. 40−43 No information in this regard is available for HCC, and we are not aware of any study reporting glycosylation changes in CFH in the context of liver disease.…”

Drusen complement components C3a and C5a promote choroidal neovascularization

“…The recent definition of complement factor H, which inhibits C3 deposition and C5a release after complement activation (31), and toll-like receptor-4, which influences C3 deposition and is negatively regulated by C5a (32,33), as major susceptibility loci in AMD (34)(35)(36)(37)(38)(39) adds to the mounting evidence of complement dysfunction in this disease. These findings and ours enrich the growing recognition that the complement system is not dedicated solely to immunological surveillance but also can play a versatile role in angiogenesis.…”

Evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer

“…In a phase II clinical trial, pancreatic cancer was shown to inhibit the MBL pathway and treatment with ω-3–rich fatty acids and gemcitabine restored MBL activity, improving patient survival [43]. In contrast, lung cancer cells evade complement-mediated cell lysis by overexpressing the alternative pathway inhibitor FH [44]. Additional studies indicate that cancer cells utilize the classical pathway to their advantage.…”