Use of Cancer-specific Yeast-secreted in Vivo Biotinylated Recombinant Antibodies for Serum Biomarker Discovery

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2008 Jul 26

PMID 18652693

Citations 13

Authors

Nathalie Scholler

Jennifer A Gross

Barbara Garvik

Lance Wells

Yan Liu

Christian M Loch

Arturo B Ramirez

Martin W McIntosh

Paul D Lampe

Nicole Urban

Affiliations

Soon will be listed here.

Abstract

Background: Strategies to discover circulating protein markers of ovarian cancer are urgently needed. We developed a novel technology that permits us to isolate recombinant antibodies directed against the potential serum biomarkers, to facilitate the further development of affinity reagents necessary to construct diagnostic tests.

Methods: This study presents a novel discovery approach based on serum immunoprecipitation with cancer-specific in vivo biotinylated recombinant antibodies (biobodies) derived from differentially selected yeast-display scFv, and analysis of the eluted serum proteins by electrophoresis and/or mass spectrometry.

Results: Using this strategy we identified catabolic fragments of complement factors, EMILIN2, Von Willebrand factor and phosphatidylethanolamine-binding protein 1 (PEBP1 or RKIP) in patient sera. To our knowledge, this is the first report of a soluble form of PEBP1 in human. Independent evidence for ovarian cancer-specific expression of PEBP1 in patient sera was found by ELISA assays and antibody arrays with anti-PEBP1 antibodies. PEBP1 was detected in 29 out of 30 ascites samples and discriminated ovarian cancer sera from controls (p = 0.02). Finally, we confirmed by western blots the presence of a 21-23 kDa fragment corresponding to the expected size of PEBP1 but we also showed additional bands of 38 kDa and 50-52 kDa in various tissues and cell lines.

Conclusion: We conclude that the novel strategy described here allows the identification of candidate biomarkers that can be variants of normally expressed proteins or that display cancer-specific post-translational modifications.

Citing Articles

A scalable hierarchical lasso for gene-environment interactions.

Zemlianskaia N, Gauderman W, Lewinger J J Comput Graph Stat. 2023; 31(4):1091-1103.

PMID: 36793591 PMC: 9928188. DOI: 10.1080/10618600.2022.2039161.

A spike protein S2 antibody efficiently neutralizes the Omicron variant.

Hu J, Chen X, Lu X, Wu L, Yin L, Zhu L Cell Mol Immunol. 2022; 19(5):644-646.

PMID: 35318422 PMC: 8938633. DOI: 10.1038/s41423-022-00847-4.

Ovarian Cancer Biomarkers: Moving Forward in Early Detection.

Bonifacio V Adv Exp Med Biol. 2020; 1219:355-363.

PMID: 32130708 DOI: 10.1007/978-3-030-34025-4_18.

Detection of Epithelial Ovarian Cancer using C8Magnetic Bead Separation and MALDI-TOF Plasma Proteome Profiling in Egyptian Females.

Rizk M, Sharaki O, Meleis M, Younan D, Elkial A, Moez P Asian Pac J Cancer Prev. 2019; 20(12):3603-3609.

PMID: 31870100 PMC: 7173393. DOI: 10.31557/APJCP.2019.20.12.3603.

Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections.

Hertz T, Beatty P, MacMillen Z, Killingbeck S, Wang C, Harris E J Immunol. 2017; 198(10):4025-4035.

PMID: 28381638 PMC: 5603231. DOI: 10.4049/jimmunol.1700029.

References

Turnberg D, Botto M . The regulation of the complement system: insights from genetically-engineered mice. Mol Immunol. 2003; 40(2-4):145-53. DOI: 10.1016/s0161-5890(03)00110-x. View

Loch C, Ramirez A, Liu Y, Sather C, Delrow J, Scholler N . Use of high density antibody arrays to validate and discover cancer serum biomarkers. Mol Oncol. 2009; 1(3):313-20. PMC: 2671017. DOI: 10.1016/j.molonc.2007.08.004. View

Walport M . Complement. First of two parts. N Engl J Med. 2001; 344(14):1058-66. DOI: 10.1056/NEJM200104053441406. View

Horstmann R, Sievertsen H, Knobloch J, Fischetti V . Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci U S A. 1988; 85(5):1657-61. PMC: 279833. DOI: 10.1073/pnas.85.5.1657. View

Peek R, Pruijn G, van Venrooij W . Epitope specificity determines the ability of anti-Ro52 autoantibodies to precipitate Ro ribonucleoprotein particles. J Immunol. 1994; 153(9):4321-9. View

Pickering M, Cook H, Warren J, Bygrave A, Moss J, Walport M . Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. Nat Genet. 2002; 31(4):424-8. DOI: 10.1038/ng912. View

Hengst U, Albrecht H, Hess D, Monard D . The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors. J Biol Chem. 2000; 276(1):535-40. DOI: 10.1074/jbc.M002524200. View

Trottein F, Cowman A . The primary structure of a putative phosphatidylethanolamine-binding protein from Plasmodium falciparum. Mol Biochem Parasitol. 1995; 70(1-2):235-9. DOI: 10.1016/0166-6851(95)00031-u. View

Matsumoto M, Takeda J, Inoue N, Hara T, Hatanaka M, Takahashi K . A novel protein that participates in nonself discrimination of malignant cells by homologous complement. Nat Med. 1997; 3(11):1266-70. DOI: 10.1038/nm1197-1266. View

10.

Bradley D, Ratcliffe O, Vincent C, Carpenter R, Coen E . Inflorescence commitment and architecture in Arabidopsis. Science. 1997; 275(5296):80-3. DOI: 10.1126/science.275.5296.80. View

11.

Keller A, Nesvizhskii A, Kolker E, Aebersold R . Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem. 2002; 74(20):5383-92. DOI: 10.1021/ac025747h. View

12.

Feldhaus M, Siegel R, Opresko L, Coleman J, Feldhaus J, Yeung Y . Flow-cytometric isolation of human antibodies from a nonimmune Saccharomyces cerevisiae surface display library. Nat Biotechnol. 2003; 21(2):163-70. DOI: 10.1038/nbt785. View

13.

Hellstrom I, Raycraft J, Hayden-Ledbetter M, Ledbetter J, Schummer M, McIntosh M . The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003; 63(13):3695-700. View

14.

MacLean B, Eng J, Beavis R, McIntosh M . General framework for developing and evaluating database scoring algorithms using the TANDEM search engine. Bioinformatics. 2006; 22(22):2830-2. DOI: 10.1093/bioinformatics/btl379. View

15.

Rauch A, Bellew M, Eng J, Fitzgibbon M, Holzman T, Hussey P . Computational Proteomics Analysis System (CPAS): an extensible, open-source analytic system for evaluating and publishing proteomic data and high throughput biological experiments. J Proteome Res. 2006; 5(1):112-21. DOI: 10.1021/pr0503533. View

16.

Scholler N, Lowe K, Bergan L, Kampani A, Ng V, Forrest R . Use of yeast-secreted in vivo biotinylated recombinant antibodies (Biobodies) in bead-based ELISA. Clin Cancer Res. 2008; 14(9):2647-55. PMC: 2744596. DOI: 10.1158/1078-0432.CCR-07-1442. View

17.

Tohdoh N, Tojo S, Agui H, Ojika K . Sequence homology of rat and human HCNP precursor proteins, bovine phosphatidylethanolamine-binding protein and rat 23-kDa protein associated with the opioid-binding protein. Brain Res Mol Brain Res. 1995; 30(2):381-4. DOI: 10.1016/0169-328x(95)00029-r. View

18.

Junnikkala S, Hakulinen J, Jarva H, Manuelian T, Bjorge L, Butzow R . Secretion of soluble complement inhibitors factor H and factor H-like protein (FHL-1) by ovarian tumour cells. Br J Cancer. 2002; 87(10):1119-27. PMC: 2376183. DOI: 10.1038/sj.bjc.6600614. View

19.

Spessotto P, Bulla R, Danussi C, Radillo O, Cervi M, Monami G . EMILIN1 represents a major stromal element determining human trophoblast invasion of the uterine wall. J Cell Sci. 2006; 119(Pt 21):4574-84. DOI: 10.1242/jcs.03232. View

20.

Pikielny C, Hasan G, Rouyer F, Rosbash M . Members of a family of Drosophila putative odorant-binding proteins are expressed in different subsets of olfactory hairs. Neuron. 1994; 12(1):35-49. DOI: 10.1016/0896-6273(94)90150-3. View