17AAG‑induced internalisation of HER2‑specific Affibody molecules

Göstring,Lovisa; Lindegren,Sture; Gedda,Lars

doi:10.3892/ol.2016.4990

17AAG‑induced internalisation of HER2‑specific Affibody molecules

Authors:
- Lovisa Göstring
- Sture Lindegren
- Lars Gedda
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Affiliations: Department of Immunology, Genetics and Pathology, Uppsala University, SE‑75185 Uppsala, Sweden, Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg, SE-41345 Gothenburg, Sweden
Published online on: August 10, 2016 https://doi.org/10.3892/ol.2016.4990
Pages: 2574-2580
Copyright: © Göstring et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation‑resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17‑AAG was used to increase internalisation of the HER2‑specific Affibody molecule ABY‑025. The cellular redistribution of halogen‑labelled 211At‑ABY‑025 and radiometal‑labelled 111In‑ABY‑025 following treatment with 17‑AAG was studied. 17‑AAG treatment of SKOV‑3 human ovarian carcinoma and SKBR‑3 human breast carcinoma cells to some extent shifted the localisation of 111In‑ABY‑025 from the cell surface to intracellular compartments in the two cell lines. ABY‑025 labelled with the high‑linear energy transfer α emitter 211At was also internalised to a higher degree; however, due to its physiological properties, this nuclide was excreted faster. The results indicate that 17‑AAG may be used to facilitate cell‑specific intracellular localisation of a suitable cytotoxic or radioactive agent coupled to ABY‑025 in HER2‑overexpressing cells.

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1	Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J and Ullrich A: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 244:707–712. 1989. View Article : Google Scholar : PubMed/NCBI
2	Carpenter G and Cohen S: 125I-labeled human epidermal growth factor. Binding, internalization and degradation in human fibroblasts. J Cell Biol. 71:159–171. 1976. View Article : Google Scholar : PubMed/NCBI
3	Stoscheck CM and Carpenter G: Down regulation of epidermal growth factor receptors: Direct demonstration of receptor degradation in human fibroblasts. J Cell Biol. 98:1048–1053. 1984. View Article : Google Scholar : PubMed/NCBI
4	Hendriks BS, Opresko LK, Wiley HS and Lauffenburger D: Coregulation of epidermal growth factor receptor/human epidermal growth factor receptor 2 (HER2) levels and locations: Quantitative analysis of HER2 overexpression effects. Cancer Res. 63:1130–1137. 2003.PubMed/NCBI
5	Hommelgaard AM, Lerdrup M and van Deurs B: Association with membrane protrusions makes ErbB2 an internalization-resistant receptor. Mol Biol Cell. 15:1557–1567. 2004. View Article : Google Scholar : PubMed/NCBI
6	Worthylake R, Opresko LK and Wiley HS: ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. J Biol Chem. 274:8865–8874. 1999. View Article : Google Scholar : PubMed/NCBI
7	Citri A, Skaria KB and Yarden Y: The deaf and the dumb: The biology of ErbB-2 and ErbB-3. Exp Cell Res. 284:54–65. 2003. View Article : Google Scholar : PubMed/NCBI
8	Tikhomirov O and Carpenter G: Geldanamycin induces ErbB-2 degradation by proteolytic fragmentation. J Biol Chem. 275:26625–26631. 2000. View Article : Google Scholar : PubMed/NCBI
9	Xu W, Mimnaugh E, Rosser MF, Nicchitta C, Marcu M, Yarden Y and Neckers L: Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90. J Biol Chem. 276:3702–3708. 2001. View Article : Google Scholar : PubMed/NCBI
10	Zhou P, Fernandes N, Dodge IL, Reddi AL, Rao N, Safran H, DiPetrillo TA, Wazer DE, Band V and Band H: ErbB2 degradation mediated by the co-chaperone protein CHIP. J Biol Chem. 278:13829–13837. 2003. View Article : Google Scholar : PubMed/NCBI
11	Raja SM, Clubb RJ, Bhattacharyya M, Dimri M, Cheng H, Pan W, Ortega-Cava C, Lakku-Reddi A, Naramura M, Band V and Band H: A combination of Trastuzumab and 17-AAG induces enhanced ubiquitinylation and lysosomal pathway-dependent ErbB2 degradation and cytotoxicity in ErbB2-overexpressing breast cancer cells. Cancer Biol Ther. 7:1630–1640. 2008. View Article : Google Scholar : PubMed/NCBI
12	Lerdrup M, Hommelgaard AM, Grandal M and van Deurs B: Geldanamycin stimulates internalization of ErbB2 in a proteasome-dependent way. J Cell Sci. 119:85–95. 2006. View Article : Google Scholar : PubMed/NCBI
13	Austin CD, De Mazière AM, Pisacane PI, van Dijk SM, Eigenbrot C, Sliwkowski MX, Klumperman J and Scheller RH: Endocytosis and sorting of ErbB2 and the site of action of cancer therapeutics trastuzumab and geldanamycin. Mol Biol Cell. 15:5268–5282. 2004. View Article : Google Scholar : PubMed/NCBI
14	Powers MV and Workman P: Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors. Endocr Relat Cancer. 13(Supply 1): S125–S135. 2006. View Article : Google Scholar : PubMed/NCBI
15	Fukuyo Y, Hunt CR and Horikoshi N: Geldanamycin and its anti-cancer activities. Cancer Lett. 290:24–35. 2010. View Article : Google Scholar : PubMed/NCBI
16	Sain N, Krishnan B, Ormerod MG, De Rienzo A, Liu WM, Kaye SB, Workman P and Jackman AL: Potentiation of paclitaxel activity by the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin in human ovarian carcinoma cell lines with high levels of activated AKT. Mol Cancer Ther. 5:1197–1208. 2006. View Article : Google Scholar : PubMed/NCBI
17	Banerji U, Sain N, Sharp SY, Valenti M, Asad Y, Ruddle R, Raynaud F, Walton M, Eccles SA, Judson I, et al: An in vitro and in vivo study of the combination of the heat shock protein inhibitor 17-allylamino-17-demethoxygeldanamycin and carboplatin in human ovarian cancer models. Cancer Chemother Pharmacol. 62:769–778. 2008. View Article : Google Scholar : PubMed/NCBI
18	Hu L, Hofmann J, Lu Y, Mills GB and Jaffe RB: Inhibition of phosphatidylinositol 3′-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Cancer Res. 62:1087–1092. 2002.PubMed/NCBI
19	Wu X, Wanders A, Wardega P, Tinge B, Gedda L, Bergstrom S, Sooman L, Gullbo J, Bergqvist M, Hesselius P, et al: Hsp90 is expressed and represents a therapeutic target in human oesophageal cancer using the inhibitor 17-allylamino-17-demethoxygeldanamycin. Br J Cancer. 100:334–343. 2009. View Article : Google Scholar : PubMed/NCBI
20	Nygren PA: Alternative binding proteins: Affibody binding proteins developed from a small three-helix bundle scaffold. FEBS J. 275:2668–2676. 2008. View Article : Google Scholar : PubMed/NCBI
21	Friedman M and Ståhl S: Engineered affinity proteins for tumour-targeting applications. Biotechnol Appl Biochem. 53:1–29. 2009. View Article : Google Scholar : PubMed/NCBI
22	Baum RP, Prasad V, Müller D, Schuchardt C, Orlova A, Wennborg A, Tolmachev V and Feldwisch J: Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules. J Nucl Med. 51:892–897. 2010. View Article : Google Scholar : PubMed/NCBI
23	Ahlgren S, Orlova A, Wallberg H, Hansson M, Sandström M, Lewsley R, Wennborg A, Abrahmsén L, Tolmachev V and Feldwisch J: Targeting of HER2-expressing tumors using 111In-ABY-025, a second-generation affibody molecule with a fund-amentally reengineered scaffold. J Nucl Med. 51:1131–1138. 2010. View Article : Google Scholar : PubMed/NCBI
24	Lindegren S, Frost S, Bäck T, Haglund E, Elgqvist J and Jensen H: Direct procedure for the production of 211At-labeled antibodies with an epsilon-lysyl-3 (trimethylstannyl)benzamide immunoconjugate. J Nucl Med. 49:1537–1545. 2008. View Article : Google Scholar : PubMed/NCBI
25	Wallberg H and Orlova A: Slow internalization of anti-HER2 synthetic affibody monomer 111In-DOTA-ZHER2:342-pep2: Implications for development of labeled tracers. Cancer Biother Radiopharm. 23:435–442. 2008. View Article : Google Scholar : PubMed/NCBI
26	Gartner EM, Silverman P, Simon M, Flaherty L, Abrams J, Ivy P and Lorusso PM: A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer. Breast Cancer Res Treat. 131(3): 933–7. 2012. View Article : Google Scholar : PubMed/NCBI
27	Pedersen KS, Kim GP, Foster NR, Wang-Gillam A, Erlichman C and McWilliams RR: Phase II trial of gemcitabine and tanespimycin (17AAG) in metastatic pancreatic cancer: a Mayo Clinic Phase II Consortium study. Invest New Drugs. 33(4): 963–8. 2015. View Article : Google Scholar : PubMed/NCBI
28	Oki Y, Copeland A, Romaguera J, Fayad L, Fanale M, Sde C Faria, Medeiros LJ, Ivy P and Younes A: Clinical experience with the heat shock protein-90 inhibitor, tanespimycin, in patients with relapsed lymphoma. Leuk Lymphoma. 53(5): 990–2. 2012. View Article : Google Scholar : PubMed/NCBI
29	Shih LB, Thorpe SR, Griffiths GL, Diril H, Ong GL, Hansen HJ, Goldenberg DM and Mattes MJ: The processing and fate of antibodies and their radiolabels bound to the surface of tumor cells in vitro: A comparison of nine radiolabels. J Nucl Med. 35:899–908. 1994.PubMed/NCBI
30	Tolmachev V: Chapter 8: Choice of Radionuclides and Radiolabelling TechniquesTargeted Radionuclide Tumor Therapy - Biological Aspects. Stigbrand T, Carlsson J and Adams GP: Springer; pp. 145–174. 2008, View Article : Google Scholar
31	Hartman T, Lundqvist H, Westlin JE and Carlsson J: Radiation doses to the cell nucleus in single cells and cells in micro-metas-tases in targeted therapy with (131)I labeled ligands or antibodies. Int J Radiat Oncol Biol Phys. 46:1025–1036. 2000. View Article : Google Scholar : PubMed/NCBI
32	Wilbur S: Chemical and Radiochemical Considerations in Radiolabeling with-Emitting Radionuclides. Current Pharmaceuticals. 4:214–247. 2011. View Article : Google Scholar