Intracellular Factor H Drives Tumor Progression Independently of the Complement Cascade.
Journal
Cancer immunology research
ISSN: 2326-6074
Titre abrégé: Cancer Immunol Res
Pays: United States
ID NLM: 101614637
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
22
09
2020
revised:
03
03
2021
accepted:
18
05
2021
pubmed:
28
5
2021
medline:
5
3
2022
entrez:
27
5
2021
Statut:
ppublish
Résumé
The complement system is a powerful and druggable innate immune component of the tumor microenvironment. Nevertheless, it is challenging to elucidate the exact mechanisms by which complement affects tumor growth. In this study, we examined the processes by which the master complement regulator factor H (FH) affects clear cell renal cell carcinoma (ccRCC) and lung cancer, two cancers in which complement overactivation predicts poor prognosis. FH was present in two distinct cellular compartments: the membranous (mb-FH) and intracellular (int-FH) compartments. Int-FH resided in lysosomes and colocalized with C3. In ccRCC and lung adenocarcinoma, FH exerted protumoral action through an intracellular, noncanonical mechanism. FH silencing in ccRCC cell lines resulted in decreased proliferation, due to cell-cycle arrest and increased mortality, and this was associated with increased p53 phosphorylation and NFκB translocation to the nucleus. Moreover, the migration of the FH-silenced cells was reduced, likely due to altered morphology. These effects were cell type-specific because no modifications occurred upon
Identifiants
pubmed: 34039652
pii: 2326-6066.CIR-20-0787
doi: 10.1158/2326-6066.CIR-20-0787
doi:
Substances chimiques
Complement Factor H
80295-65-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
909-925Subventions
Organisme : Wellcome Trust
ID : 212252/Z/18/Z
Pays : United Kingdom
Informations de copyright
©2021 American Association for Cancer Research.
Références
Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I - molecular mechanisms of activation and regulation. Front Immunol. 2015;6:262.
Merle NS, Noe R, Halbwachs-Mecarelli L, Fremeaux-Bacchi V, Roumenina LT. Complement system part II: role in immunity. Front Immunol. 2015;6:257.
Ricklin D, Mastellos DC, Reis ES, Lambris JD. The renaissance of complement therapeutics. Nat Rev Nephrol. 2018;14:26–47.
Roumenina LT, Daugan MV, Petitprez F, Sautès-Fridman C, Fridman WH. Context-dependent roles of complement in cancer. Nat Rev Cancer. 2019;19:698–715.
Lubbers R, van Essen MF, van Kooten C, Trouw LA. Production of complement components by cells of the immune system. Clin Exp Immunol. 2017;188:183–94.
Bulla R, Tripodo C, Rami D, Ling GS, Agostinis C, Guarnotta C, et al. C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation. Nat Commun. 2016;7:10346.
Roumenina LT, Daugan MV, Noe R, Petitprez F, Vano YA, Sanchez-Salas R, et al. Tumor cells hijack macrophage-produced complement C1q to promote tumor growth. Cancer Immunol Res. 2019;7:1091–1105.
Al-Adnani MS, McGEE JO. C1q production and secretion by fibroblasts. Nature. 1976;263:145–6.
Kesselring R, Thiel A, Pries R, Fichtner-Feigl S, Brunner S, Seidel P, et al. The complement receptors CD46, CD55 and CD59 are regulated by the tumour microenvironment of head and neck cancer to facilitate escape of complement attack. Eur J Cancer. 2014;50:2152–61.
Ajona D, Castaño Z, Garayoa M, Zudaire E, Pajares MJ, Martinez A, et al. Expression of complement factor H by lung cancer cells: effects on the activation of the alternative pathway of complement. Cancer Res. 2004;64:6310–8.
Fishelson Z, Kirschfink M. Complement C5b-9 and cancer: mechanisms of cell damage, cancer counteractions, and approaches for intervention. Front Immunol. 2019;10:752.
Bushey RT, Moody MA, Nicely NL, Haynes BF, Alam SM, Keir ST, et al. A therapeutic antibody for cancer, derived from single human B cells. Cell Rep. 2016;15:1505–13.
Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, et al. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell. 2015;160:700–14.
Laskowski J, Renner B, Pickering MC, Serkova NJ, Smith-Jones PM, Clambey ET, et al. Complement factor H–deficient mice develop spontaneous hepatic tumors. J Clin Invest. 2020;130:4039–4054.
Arbore G, Kemper C, Kolev M. Intracellular complement - the complosome - in immune cell regulation. Mol Immunol. 2017;89:2–9.
Junnikkala S, Hakulinen J, Jarva H, Manuelian T, Bjørge L, Bützow R, et al. Secretion of soluble complement inhibitors factor H and factor H-like protein (FHL-1) by ovarian tumour cells. Br J Cancer. 2002;87:1119–27.
Gasque P, Julen N, Ischenko AM, Picot C, Mauger C, Chauzy C, et al. Expression of complement components of the alternative pathway by glioma cell lines. J Immunol. 1992;149:1381–7.
Junnikkala S, Jokiranta TS, Friese MA, Jarva H, Zipfel PF, Meri S. Exceptional resistance of human H2 glioblastoma cells to complement-mediated killing by expression and utilization of factor H and factor H-like protein 1. J Immunol. 2000;164:6075–81.
Riihilä PM, Nissinen LM, Ala-aho R, Kallajoki M, Grénman R, Meri S, et al. Complement factor H: a biomarker for progression of cutaneous squamous cell carcinoma. J Invest Dermatol. 2014;134:498–506.
Smolag KI, Mueni CM, Leandersson K, Jirström K, Hagerling C, Mörgelin M, et al. Complement inhibitor factor H expressed by breast cancer cells differentiates CD14+ human monocytes into immunosuppressive macrophages. Oncoimmunology. 2020;9:1731135.
Liszewski MK, Kolev M, Le Friec G, Leung M, Bertram PG, Fara AF, et al. Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation. Immunity. 2013;39:1143–57.
West EE, Kolev M, Kemper C. Complement and the regulation of T cell responses. Annu Rev Immunol. 2018;36:309–38.
King BC, Kulak K, Krus U, Rosberg R, Golec E, Wozniak K, et al. Complement component C3 is highly expressed in human pancreatic islets and prevents β cell death via ATG16L1 interaction and autophagy regulation. Cell Metab. 2019;29:202–10.
Józsi M, Schneider AE, Kárpáti É, Sándor N. Complement factor H family proteins in their non-canonical role as modulators of cellular functions. Semin Cell Dev Biol. 2019;85:122–31.
Seol HS, Lee SE, Song JS, Rhee Je-K, Singh SR, Chang S, et al. Complement proteins C7 and CFH control the stemness of liver cancer cells via LSF-1. Cancer Lett. 2016;372:24–35.
Vernon KA, Ruseva MM, Cook HT, Botto M, Malik TH, Pickering MC. Partial complement factor H deficiency associates with C3 glomerulopathy and thrombotic microangiopathy. J Am Soc Nephrol. 2016;27:1334–42.
Daugan MV, Revel M, Lacroix L, Sautès-Fridman C, Fridman WH, Roumenina LT. Complement detection in human tumors by immunohistochemistry and immunofluorescence. Methods Mol Biol. 2021;2227:191–203.
Dragon-Durey MA, Frémeaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschenes G, et al. Heterozygous and homozygous factor h deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases. J Am Soc Nephrol. 2004;15:787–95.
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.
Trouw LA, Bengtsson AA, Gelderman KA, Dahlbäck B, Sturfelt G, Blom AM. C4b-binding protein and factor H compensate for the loss of membrane-bound complement inhibitors to protect apoptotic cells against excessive complement attack. J Biol Chem. 2007;282:28540–8.
Leffler J, Herbert AP, Norström E, Schmidt CQ, Barlow PN, Blom AM, et al. Annexin-II, DNA, and histones serve as factor H ligands on the surface of apoptotic cells. J Biol Chem. 2010;285:3766–76.
Lovell M, Lott ST, Wong P, El-Naggar A, Tucker S, Killary AM. The genetic locus NRC-1 within chromosome 3p12 mediates tumor suppression in renal cell carcinoma independently of histological type, tumor microenvironment, and VHL mutation. Cancer Res. 1999;59:2182–9.
Ajona D, Hsu YF, Corrales L, Montuenga LM, Pio R. Down-regulation of human complement factor H sensitizes non-small cell lung cancer cells to complement attack and reduces in vivo tumor growth. J Immunol. 2007;178:5991–8.
Liu J, Hoh J. Loss of complement factor H in plasma increases endothelial cell migration. J Cancer. 2017;8:2184–90.
Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, et al. Modulation of the antitumor immune response by complement. Nat Immunol. 2008;9:1225–35.
Daugan MV, Revel M, Russick J, Dragon-Durey MA, Gaboriaud C, Robe-Rybkine T, et al. Complement C1s and C4d as prognostic biomarkers in renal cancer: emergence of noncanonical functions of C1s. Cancer Immunol Res. 2021;9:891–908.
Martin M, Leffler J, Smoląg KI, Mytych J, Björk A, Chaves LD, et al. Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes. Cell Death Differ. 2016;23:903–11.
Boudhabhay I, Poillerat V, Grunenwald A, Torset C, Leon J, Daugan MV, et al. Complement activation is a crucial driver of acute kidney injury in rhabdomyolysis. Kidney Int. 2021;99:581–97.
Merle NS, Leon J, Poillerat V, Grunenwald A, Boudhabhay I, Knockaert S, et al. Circulating FH protects kidneys from tubular injury during systemic hemolysis. Front Immunol. 2020;11:1772.
Corrales L, Ajona D, Rafail S, Lasarte JJ, Riezu-Boj JI, Lambris JD, et al. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression. J Immunol. 2012;189:4674–83.
Ajona D, Pajares MJ, Corrales L, Perez-Gracia JL, Agorreta J, Lozano MD, et al. Investigation of complement activation product C4d as a diagnostic and prognostic biomarker for lung cancer. J Natl Cancer Inst. 2013;105:1385–93.
Ajona D, Okrój M, Pajares MJ, Agorreta J, Lozano MD, Zulueta JJ, et al. Complement C4d-specific antibodies for the diagnosis of lung cancer. Oncotarget. 2017;9:6346–55.
Reese B, Silwal A, Daugherity E, Daugherity M, Arabi M, Daly P, et al. Complement as prognostic biomarker and potential therapeutic target in renal cell carcinoma. J Immunol. 2020;205:3218–29.
Motzer RJ, Banchereau R, Hamidi H, Powles T, McDermott D, Atkins MB, et al. Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis blockade. Cancer Cell. 2020;38:803–17.
Cui T, Chen Y, Knösel T, Yang L, Zöller K, Galler K, et al. Human complement factor H is a novel diagnostic marker for lung adenocarcinoma. Int J Oncol. 2011;39:161–8.
Okemefuna AI, Nan R, Gor J, Perkins SJ. Electrostatic interactions contribute to the folded-back conformation of wild type human factor H. J Mol Biol. 2009;391:98–118.
Sim E, Sim RB. Enzymic assay of C3b receptor on intact cells and solubilized cells. Biochem J. 1983;210:567–76.
Kask L, Villoutreix BO, Steen M, Ramesh B, Dahlbäck B, Blom AM. Structural stability and heat-induced conformational change of two complement inhibitors: C4b-binding protein and factor H. Protein Sci. 2004;13:1356–64.
Kastenhuber ER, Lowe SW. Putting p53 in context. Cell. 2017;170:1062–78.
Carrà G, Lingua MF, Maffeo B, Taulli R, Morotti A. P53 vs NF-κB: the role of nuclear factor-kappa B in the regulation of p53 activity and vice versa. Cell Mol Life Sci. 2020;77:4449–58.
Campa MJ, Gottlin EB, Bushey RT, Patz EF. Complement factor H antibodies from lung cancer patients induce complement-dependent lysis of tumor cells, suggesting a novel immunotherapeutic strategy. Cancer Immunol Res. 2015;3:1325–32.
Krilis M, Qi M, Qi J, Wong JWH, Guymer R, Liew G, et al. Dual roles of different redox forms of complement factor H in protecting against age related macular degeneration. Free Radic Biol Med. 2018;129:237–46.
Amornsiripanitch N, Hong S, Campa MJ, Frank MM, Gottlin EB, Patz EF. Complement factor H autoantibodies are associated with early stage NSCLC. Clin Cancer Res. 2010;16:3226–31.
Kwak JW, Laskowski J, Li HY, McSharry MV, Sippel TR, Bullock BL, et al. Complement activation via a C3a receptor pathway alters CD4+ T lymphocytes and mediates lung cancer progression. Cancer Res. 2018;78:143–56.
Tsokos GC, Inghirami G, Tsoukas CD, Balow JE, Lambris JD. Regulation of immunoglobulin secretion by factor H of human complement. Immunology. 1985;55:419–26.
Nabil K, Rihn B, Jaurand M-C, Vignaud J-M, Ripoche J, Martinet Y, et al. Identification of human complement factor H as a chemotactic protein for monocytes. Biochem J. 1997;326:377–83.
Ohtsuka H, Imamura T, Matsushita M, Tanase S, Okada H, Ogawa M, et al. Thrombin generates monocyte chemotactic activity from complement factor H. Immunology. 1993;80:140–5.
Olivar R, Luque A, Cárdenas-Brito S, Naranjo-Gómez M, Blom AM, Borràs FE, et al. The complement inhibitor factor H generates an anti-inflammatory and tolerogenic state in monocyte-derived dendritic cells. J Immunol. 2016;196:4274–90.
Dixon KO, O'Flynn J, Klar-Mohamad N, Daha MR, van Kooten C. Properdin and factor H production by human dendritic cells modulates their T-cell stimulatory capacity and is regulated by IFN-γ. Eur J Immunol. 2017;47:470–80.
Schneider AE, Sándor N, Kárpáti É, Józsi M. Complement factor H modulates the activation of human neutrophil granulocytes and the generation of neutrophil extracellular traps. Mol Immunol. 2016;72:37–48.
Hallam D, Collin J, Bojic S, Chichagova V, Buskin A, Xu Y, et al. An induced pluripotent stem cell patient specific model of complement factor H (Y402H) polymorphism displays characteristic features of age-related macular degeneration and indicates a beneficial role for UV light exposure. Stem Cells. 2017;35:2305–20.
Wu J, Xie X, Nie S, Buckanovich RJ, Lubman DM. Altered expression of sialylated glycoproteins in ovarian cancer sera using lectin-based ELISA assay and quantitative glycoproteomics analysis. J Proteome Res. 2013;12:3342–52.
Benicky J, Sanda M, Pompach P, Wu J, Goldman R. Quantification of fucosylated hemopexin and complement factor H in plasma of patients with liver disease. Anal Chem. 2014;86:10716–23.
Yang JD, Seol SY, Leem SH, Kim YH, Sun Z, Lee JS, et al. Genes associated with recurrence of hepatocellular carcinoma: integrated analysis by gene expression and methylation profiling. J Korean Med Sci. 2011;26:1428–38.