Cell Growth Inhibition and Apoptotic Effects of a Specific Anti-RTFscFv Antibody on Prostate Cancer, but Not Glioblastoma, Cells

Overview

Journal F1000Res

Specialties Biomedical Engineering
Science

Date 2017 May 12

PMID 28491282

Citations 6

Authors

Foroogh Nejatollahi

Payam Bayat

Bahareh Moazen

Affiliations

Soon will be listed here.

Abstract

Single chain antibody (scFv) has shown interesting results in cancer immunotargeting approaches, due to its advantages over monoclonal antibodies. Regeneration and tolerance factor (RTF) is one of the most important regulators of extracellular and intracellular pH in eukaryotic cells. In this study, the inhibitory effects of a specific anti-RTF scFv were investigated and compared between three types of prostate cancer and two types of glioblastoma cells. A phage antibody display library of scFv was used to select specific scFvs against RTF using panning process. The reactivity of a selected scFv was assessed by phage ELISA. The anti-proliferative and apoptotic effects of the antibody on prostate cancer (PC-3, Du-145 and LNCaP) and glioblastoma (U-87 MG and A-172) cell lines were investigated by MTT and Annexin V/PI assays. A specific scFv with frequency 35% was selected against RTF epitope. This significantly inhibited the proliferation of the prostate cells after 24 h. The percentages of cell viability (using 1000 scFv/cell) were 52, 61 and 73% for PC-3, Du-145 and LNCaP cells, respectively, compared to untreated cells. The antibody (1000 scFv/cell) induced apoptosis at 50, 40 and 25% in PC-3, Du-145 and LNCaP cells, respectively. No growth inhibition and apoptotic induction was detected for U-87 and A172 glioblastoma cells. Anti-RTFscFv significantly reduced the proliferation of the prostate cancer cells. The inhibition of cell growth and apoptotic induction effects in PC-3 cells were greater than Du-145 and LNCaP cells. This might be due to higher expression of RTF antigen in PC-3 cells and/or better accessibility of RTF to scFv antibody. The resistance of glioblastoma cells to anti-RTF scFv offers the existence of mechanism(s) that abrogate the inhibitory effect(s) of the antibody to RTF. The results suggest that the selected anti-RTF scFv antibody could be an effective new alternative for prostate cancer immunotherapy.

Citing Articles

Novel single-chain antibodies against highly conserved epitopes in the hemagglutinin of influenza A viruses: Promising agents for universal therapies.

Alizadeh S, Moazen S, Nooreddin Faraji S, Moattari A, Nejatollahi F Iran J Basic Med Sci. 2021; 24(1):17-23.

PMID: 33643565 PMC: 7894632. DOI: 10.22038/ijbms.2020.43508.10219.

Anti-Proliferative Effect of Specific Anti-EGFR Single Chain Antibody on Triple Negative Breast Cancer Cells.

Abdollahzadeh F, Nejatollahi F Rep Biochem Mol Biol. 2020; 9(2):180-187.

PMID: 33178867 PMC: 7603265. DOI: 10.29252/rbmb.9.2.180.

Isolation of Specific Human Recombinant Antibodies Against Glycoprotein 41 of HIV.

Aghaei Afshar M, Robati R, Nejatollahi F Rep Biochem Mol Biol. 2020; 8(3):310-317.

PMID: 32274403 PMC: 7103076.

Isolation of Neutralizing Human Single Chain Antibodies Against Conserved Hemagglutinin Epitopes of Influenza a Virus H3N2 Strain.

Poursiami M, Moazen S, Nejatollahi F, Moatari A Rep Biochem Mol Biol. 2020; 8(3):301-309.

PMID: 32274402 PMC: 7103075.

Selection and Evaluation of Specific Single Chain Antibodies against CD90, a Marker for Mesenchymal and Cancer Stem Cells.

Moazen B, Zarrinhaghighi A, Nejatollahi F Rep Biochem Mol Biol. 2018; 7(1):45-51.

PMID: 30324117 PMC: 6175597.

References

Amer M . Gene therapy for cancer: present status and future perspective. Mol Cell Ther. 2015; 2:27. PMC: 4452068. View

Parker S, Diaz I, Anderson K, Batt C . Design, production, and characterization of a single-chain variable fragment (ScFv) derived from the prostate specific membrane antigen (PSMA) monoclonal antibody J591. Protein Expr Purif. 2013; 89(2):136-45. DOI: 10.1016/j.pep.2013.02.016. View

McLean L, Roscoe J, Jorgensen N, Gorin F, Cala P . Malignant gliomas display altered pH regulation by NHE1 compared with nontransformed astrocytes. Am J Physiol Cell Physiol. 2001; 278(4):C676-88. DOI: 10.1152/ajpcell.2000.278.4.C676. View

Westdorp H, Skold A, Snijer B, Franik S, Mulder S, Major P . Immunotherapy for prostate cancer: lessons from responses to tumor-associated antigens. Front Immunol. 2014; 5:191. PMC: 4018526. DOI: 10.3389/fimmu.2014.00191. View

Sennoune S, Bakunts K, Martinez G, Chua-Tuan J, Kebir Y, Attaya M . Vacuolar H+-ATPase in human breast cancer cells with distinct metastatic potential: distribution and functional activity. Am J Physiol Cell Physiol. 2004; 286(6):C1443-52. DOI: 10.1152/ajpcell.00407.2003. View

Nejatollahi F, Ranjbar R, Younesi V, Asgharpour M . Deregulation of HER2 downstream signaling in breast cancer cells by a cocktail of anti-HER2 scFvs. Oncol Res. 2013; 20(8):333-40. DOI: 10.3727/096504013X13657689382734. View

Nejatollahi F, Jaberipour M, Asgharpour M . Triple blockade of HER2 by a cocktail of anti-HER2 scFv antibodies induces high antiproliferative effects in breast cancer cells. Tumour Biol. 2014; 35(8):7887-95. DOI: 10.1007/s13277-014-1854-8. View

Neves H, Kwok H . Recent advances in the field of anti-cancer immunotherapy. BBA Clin. 2015; 3:280-8. PMC: 4661591. DOI: 10.1016/j.bbacli.2015.04.001. View

Boomer J, Lee G, Givens T, Gilman-Sachs A, Beaman K . Regeneration and tolerance factor's potential role in T-cell activation and apoptosis. Hum Immunol. 2000; 61(10):959-71. DOI: 10.1016/s0198-8859(00)00163-4. View

10.

Vaday G, Hua S, Peehl D, Pauling M, Lin Y, Zhu L . CXCR4 and CXCL12 (SDF-1) in prostate cancer: inhibitory effects of human single chain Fv antibodies. Clin Cancer Res. 2004; 10(16):5630-9. DOI: 10.1158/1078-0432.CCR-03-0633. View

11.

Younesi V, Nejatollahi F . Induction of anti-proliferative and apoptotic effects by anti-IL-25 receptor single chain antibodies in breast cancer cells. Int Immunopharmacol. 2014; 23(2):624-32. DOI: 10.1016/j.intimp.2014.10.015. View

12.

Nejatollahi F, Bayat P, Moazen B . Cell growth inhibition and apoptotic effects of a specific anti-RTFscFv antibody on prostate cancer, but not glioblastoma, cells. F1000Res. 2017; 6:156. PMC: 5399964. DOI: 10.12688/f1000research.10803.1. View

13.

Day C, Fanger G, Retter M, Hylander B, Penetrante R, Houghton R . Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera. Oncogene. 2002; 21(46):7114-20. DOI: 10.1038/sj.onc.1205786. View

14.

Mukherji D, Temraz S, Wehbe D, Shamseddine A . Angiogenesis and anti-angiogenic therapy in prostate cancer. Crit Rev Oncol Hematol. 2013; 87(2):122-31. DOI: 10.1016/j.critrevonc.2013.01.002. View

15.

Ahmad Z, Yeap S, Ali A, Ho W, Mohamed Alitheen N, Hamid M . scFv antibody: principles and clinical application. Clin Dev Immunol. 2012; 2012:980250. PMC: 3312285. DOI: 10.1155/2012/980250. View

16.

Sennoune S, Luo D, Martinez-Zaguilan R . Plasmalemmal vacuolar-type H+-ATPase in cancer biology. Cell Biochem Biophys. 2004; 40(2):185-206. DOI: 10.1385/CBB:40:2:185. View

17.

Mishima K, Kato Y, Kaneko M, Nishikawa R, Hirose T, Matsutani M . Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression. Acta Neuropathol. 2006; 111(5):483-8. DOI: 10.1007/s00401-006-0063-y. View

18.

Vieweg J . Immunotherapy for advanced prostate cancer. Rev Urol. 2007; 9 Suppl 1:S29-38. PMC: 1831540. View

19.

Mohammadi M, Nejatollahi F, Ghasemi Y, Faraji S . Anti-Metastatic and Anti-Invasion Effects of a Specific Anti-MUC18 scFv Antibody on Breast Cancer Cells. Appl Biochem Biotechnol. 2016; 181(1):379-390. DOI: 10.1007/s12010-016-2218-1. View

20.

Weller M, Frei K, Groscurth P, Krammer P, Yonekawa Y, Fontana A . Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines. J Clin Invest. 1994; 94(3):954-64. PMC: 295136. DOI: 10.1172/JCI117462. View