Gene knockdown by EpCAM aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells

Molecular Cancer Therapeutics

Volumn 14, Issue 10, 2015, Pages 2279-2291

  Gilboa Geffen, Adi ^a   Hamar, Peter ^a,b   Le, Minh T N ^a   Wheeler, Lee Adam ^a   Trifonova, Radiana ^a   Petrocca, Fabio ^a   Wittrup, Anders ^a   Lieberman, Judy ^a  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b SEMMELWEIS UNIVERSITY   (Hungary)

Author keywords

[No Author keywords available]

Indexed keywords

EPITHELIAL CELL ADHESION MOLECULE; SMALL INTERFERING RNA; APTAMER; CELL ADHESION MOLECULE; CELL CYCLE PROTEIN; EPCAM PROTEIN, HUMAN; ONCOPROTEIN; POLO-LIKE KINASE 1; PROTEIN SERINE THREONINE KINASE; TUMOR ANTIGEN;

ANIMAL CELL; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BREAST CANCER; BREAST CANCER CELL LINE; CHIMERA; CONTROLLED STUDY; FEMALE; FLOW CYTOMETRY; GENE EXPRESSION; GENE SILENCING; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; MOUSE; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; PRIORITY JOURNAL; TRIPLE NEGATIVE BREAST CANCER; TUMOR BIOPSY; TUMOR CELL; TUMOR INITIATING CELL; ANIMAL; BREAST TUMOR; CANCER STEM CELL; CANCER TRANSPLANTATION; CARCINOGENESIS; GENETICS; METABOLISM; NEOPLASM; NUCLEOTIDE SEQUENCE; NUDE MOUSE; PATHOLOGY; PHYSIOLOGY; RNA INTERFERENCE; TUMOR CELL LINE; TUMOR VOLUME;

ANIMALS; ANTIGENS, NEOPLASM; APTAMERS, NUCLEOTIDE; BASE SEQUENCE; BREAST NEOPLASMS; CARCINOGENESIS; CELL ADHESION MOLECULES; CELL CYCLE PROTEINS; CELL LINE, TUMOR; EPITHELIAL CELL ADHESION MOLECULE; FEMALE; GENE EXPRESSION; GENE KNOCKDOWN TECHNIQUES; HUMANS; MICE, NUDE; NEOPLASM TRANSPLANTATION; NEOPLASMS, GLANDULAR AND EPITHELIAL; NEOPLASTIC STEM CELLS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; RNA INTERFERENCE; RNA, SMALL INTERFERING; TUMOR BURDEN;

EID: 84934307591     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-15-0201-T     Document Type: Article

References (51)

1. de Fougerolles A, Vornlocher HP, Maraganore J, Lieberman J. Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 2007;6:443-53.
2. Tabernero J, Shapiro GI, LoRusso PM, Cervantes A, Schwartz GK, Weiss GJ, et al. First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Discov 2013;3:406-17.
3. Adams D, Coehlo T, Suhr O, Conceicao I, Waddington-Cruz M, Schmidt H, et al. Interim Results for Phase II Trial of ALN-TTR02, a Novel RNAi Therapeutic for the Treatment of Familial Amyloidotic Polyneuropathy. Biennial Meeting of the Peripheral Nerve Society, St Malo, France 2013. [updated 2013 Jun 30; cited 2015 Aug 23]. Available from: http://www.alnylam.com/capella/presentations/aln-ttr02phiidata/.
4. Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet 2014; 383:60-8.
5. Sorensen B, Mant T, Georgiev P, Rangarajan S, Pasi KJ, Creagh D, et al. A Subcutaneously Administered Investigational RNAi Therapeutic (ALNAT3) Targeting Antithrombin for Treatment of Hemophilia: Phase 1 Study Results in Subjects with Hemophilia A or B. International Society of Thrombosis and Hemostasis, Toronto, Canada. 2015. [updated 2015 Jun 23; cited 2015 Aug 23]. Available from: http://www.alnylam.com/capella/presentations/aln-at3-isth-june2015/.
6. Petrocca F, Lieberman J. Promise and challenge of RNA interference-based therapy for cancer. J Clin Oncol 2011;29:747-54.
7. Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med 2010;363:1938-48.
8. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011;121: 2750-67.
9. Metzger-Filho O, Tutt A, de Azambuja E, Saini KS, Viale G, Loi S, et al. Dissecting the heterogeneity of triple-negative breast cancer. J Clin Oncol 2012;30:1879-87.
10. McNamara JO II, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, et al. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 2006;24:1005-15.
11. Dassie JP, Liu XY, Thomas GS, Whitaker RM, Thiel KW, Stockdale KR, et al. Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nat Biotechnol 2009;27:839-49.
12. Zhou J, Li H, Li S, Zaia J, Rossi JJ. Novel dual inhibitory function aptamersiRNA delivery system for HIV-1 therapy. Mol Ther 2008;16:1481-9.
13. Neff CP, Zhou J, Remling L, Kuruvilla J, Zhang J, Li H, et al. An aptamersiRNA chimera suppresses HIV-1 viral loads and protects from helper CD4 (+) T cell decline in humanized mice. Sci Transl Med 2011;3:66ra66.
14. Kim MY, Jeong S. In vitro selection of RNA aptamer and specific targeting of ErbB2 in breast cancer cells. Nucleic Acid Ther 2011;21:173-8.
15. Wheeler LA, Trifonova R, Vrbanac V, Basar E, McKernan S, Xu Z, et al. Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimeras. J Clin Invest 2011;121:2401-12.
16. Thiel KW, Hernandez LI, Dassie JP, Thiel WH, Liu X, Stockdale KR, et al. Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers. Nucleic Acids Res 2012;40:6319-37.
17. Pastor F, Kolonias D, Giangrande PH, Gilboa E. Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay. Nature 2010;465:227-30.
18. Wheeler LA, Vrbanac V, Trifonova R, Brehm MA, Gilboa-Geffen A, Tanno S, et al. Durable knockdown and protection from HIV transmission in humanized mice treated with gel-formulated CD4 aptamer-siRNA chimeras. Mol Ther 2013;21:1378-89.
19. Shigdar S, Lin J, Yu Y, Pastuovic M, Wei M, Duan W. RNA aptamer against a cancer stem cell marker epithelial cell adhesion molecule. Cancer Sci 2011;102:991-8.
20. Stingl J, Eaves CJ, Zandieh I, Emerman JT. Characterization of bipotent mammary epithelial progenitor cells in normal adult human breast tissue. Breast Cancer Res Treat 2001;67:93-109.
21. Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, et al. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res 2004;64:5818-24.
22. Marhaba R, Klingbeil P, Nuebel T, Nazarenko I, Buechler MW, Zoeller M. CD44 and EpCAM: cancer-initiating cell markers. Curr Mol Med 2008; 8:784-804.
23. Spizzo G, Fong D, Wurm M, Ensinger C, Obrist P, Hofer C, et al. EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis. J Clin Pathol 2011;64:415-20.
24. Sarrio D, Franklin CK, Mackay A, Reis-Filho JS, Isacke CM. Epithelial and mesenchymal subpopulations within normal basal breast cell lines exhibit distinct stem cell/progenitor properties. Stem Cells 2012;30:292-303.
25. Soysal SD, Muenst S, Barbie T, Fleming T, Gao F, Spizzo G, et al. EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2(+), basal-like, and HER2 intrinsic subtypes of breast cancer. Br J Cancer 2013;108:1480-7.
26. Imrich S, Hachmeister M, Gires O. EpCAM and its potential role in tumorinitiating cells. Cell Adh Migr 2012;6:30-8.
27. Munz M, Baeuerle PA, Gires O. The emerging role of EpCAM in cancer and stem cell signaling. Cancer Res 2009;69:5627-9.
28. Federici G, Espina V, Liotta L, Edmiston KH. Breast cancer stem cells: a new target for therapy. Oncology 2011;25:25-8, 30.
29. Ladwein M, Pape UF, Schmidt DS, Schnolzer M, Fiedler S, Langbein L, et al. The cell-cell adhesion molecule EpCAM interacts directly with the tight junction protein claudin-7. Exp Cell Res 2005;309:345-57.
30. Gonzalez B, Denzel S, Mack B, Conrad M, Gires O. EpCAM is involved in maintenance of the murine embryonic stem cell phenotype. Stem Cells 2009;27:1782-91.
31. Lu TY, Lu RM, Liao MY, Yu J, Chung CH, Kao CF, et al. Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells. J Biol Chem 2010;285:8719-32.
32. Schulze K, Gasch C, Staufer K, Nashan B, Lohse AW, Pantel K, et al. Presence of EpCAM-positive circulating tumor cells as biomarker for systemic disease strongly correlates to survival in patients with hepatocellular carcinoma. Int J Cancer 2013;133:2165-71.
33. Konigsberg R, Obermayr E, Bises G, Pfeiler G, Gneist M, Wrba F, et al. Detection of EpCAM positive and negative circulating tumor cells in metastatic breast cancer patients. Acta Oncol 2011;50:700-10.
34. Weissenstein U, Schumann A, Reif M, Link S, Toffol-Schmidt UD, Heusser P. Detection of circulating tumor cells in blood of metastatic breast cancer patients using a combination of cytokeratin and EpCAM antibodies. BMC Cancer 2012;12:206.
35. Zhao S, Yang H, Zhang M, Zhang D, Liu Y, Song Y, et al. Circulating tumor cells (CTCs) detected by triple-marker EpCAM, CK19, and hMAM RT-PCR and their relation to clinical outcome in metastatic breast cancer patients. Cell Biochem Biophys 2013;65:263-73.
36. Chen Q, Ge F, Cui W, Wang F, Yang Z, Guo Y, et al. Lung cancer circulating tumor cells isolated by the EpCAM-independent enrichment strategy correlate with Cytokeratin 19-derived CYFRA21-1 and pathological staging. Clin Chim Acta 2013;419:57-61.
37. Schmidt M, Scheulen ME, Dittrich C, Obrist P, Marschner N, Dirix L, et al. An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer. Ann Oncol 2010;21:275-82.
38. Marschner N, Ruttinger D, Zugmaier G, Nemere G, Lehmann J, Obrist P, et al. Phase II study of the human anti-epithelial cell adhesion molecule antibody adecatumumab in prostate cancer patients with increasing serum levels of prostate-specific antigen after radical prostatectomy. Urol Int 2010;85:386-95.
39. Schmidt M, Ruttinger D, Sebastian M, Hanusch CA, Marschner N, Baeuerle PA, et al. Phase IB study of the EpCAM antibody adecatumumab combined with docetaxel in patients with EpCAM-positive relapsed or refractory advanced-stage breast cancer. Ann Oncol 2012;23:2306-13.
40. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 2012;483:603-7.
41. Ince TA, Richardson AL, Bell GW, Saitoh M, Godar S, Karnoub AE, et al. Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes. Cancer Cell 2007;12:160-70.
42. Daniels DA, Chen H, Hicke BJ, Swiderek KM, Gold L. A tenascin-C aptamer identified by tumor cell SELEX: systematic evolution of ligands by exponential enrichment. Proc Natl Acad Sci U S A 2003;100:15416-21.
43. Huang Z, Szostak JW. Evolution of aptamers with a new specificity and new secondary structures from an ATP aptamer. RNA 2003;9:1456-63.
44. Gold L, Janjic N, Jarvis T, Schneider D, Walker JJ, Wilcox SK, et al. Aptamers and the RNA world, past and present. Cold Spring Harb Perspect Biol 2012;4:a003582.
45. Zimmermann B, Gesell T, Chen D, Lorenz C, Schroeder R. Monitoring genomic sequences during SELEX using high-throughput sequencing: neutral SELEX. PLoS ONE 2010;5:e9169.
46. Burnett JC, Rossi JJ. RNA-based therapeutics: current progress and future prospects. Chem Biol 2012;19:60-71.
47. Dassie JP, Giangrande PH. Current progress on aptamer-targeted oligonucleotide therapeutics. Ther Deliv 2013;4:1527-46.
48. Keefe AD, Pai S, Ellington A. Aptamers as therapeutics. Nat Rev Drug Discov 2010;9:537-50.
49. Sundaram P, Kurniawan H, Byrne ME, Wower J. Therapeutic RNAaptamers in clinical trials. Eur J Pharm Sci 2013;48:259-71.
50. Kotula JW, Pratico ED, Ming X, Nakagawa O, Juliano RL, Sullenger BA. Aptamer-mediated delivery of splice-switching oligonucleotides to the nuclei of cancer cells. Nucleic Acid Ther 2012;22:187-95.
51. Esposito CL, Cerchia L, Catuogno S, De Vita G, Dassie JP, Santamaria G, et al. Multifunctional aptamer-miRNA conjugates for targeted cancer therapy. Mol Ther 2014;22:1151-63.