Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion

Oncotarget

Volumn 6, Issue 37, 2015, Pages 40310-40326

  Henry, Claire ^a   Llamosas, Estelle ^a   Knipprath Meszaros, Alexandra ^b   Schoetzau, Andreas ^b   Obermann, Ellen ^b   Fuenfschilling, Maya ^b   Caduff, Rosemarie ^c   Fink, Daniel ^d   Hacker, Neville ^e   Ward, Robyn ^f   Heinzelmann Schwarz, Viola ^b   Ford, Caroline ^a  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b UNIVERSITY HOSPITAL BASEL   (Switzerland)

^c UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^d UNIVERSITÄTSSPITAL ZÜRICH   (Switzerland)

^e ROYAL HOSPITAL FOR WOMEN   (Australia)

^f UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Epithelial ovarian cancer; Metastasis; ROR1; ROR2; Wnt signalling

Indexed keywords

RECEPTOR TYROSINE KINASE LIKE ORPHAN RECEPTOR; RECEPTOR TYROSINE KINASE LIKE ORPHAN RECEPTOR 1; RECEPTOR TYROSINE KINASE LIKE ORPHAN RECEPTOR 2; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; ONCOPROTEIN; ROR1 PROTEIN, HUMAN; ROR2 PROTEIN, HUMAN; WNT PROTEIN; WNT5A PROTEIN; WNT5A PROTEIN, HUMAN;

ARTICLE; CANCER INHIBITION; CELL ADHESION; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; COHORT ANALYSIS; CONTROLLED STUDY; EXTRACELLULAR MATRIX; FEMALE; HUMAN; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; MAJOR CLINICAL STUDY; OVARY CARCINOMA; PROTEIN EXPRESSION; PROTEIN TARGETING; CELL MOTION; DISEASE FREE SURVIVAL; GENE EXPRESSION REGULATION; GENETICS; IMMUNOBLOTTING; METABOLISM; NEOPLASM; OVARY TUMOR; PATHOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA INTERFERENCE; TUMOR CELL LINE; TUMOR INVASION; TUMOR RECURRENCE;

CELL ADHESION; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; COHORT STUDIES; DISEASE-FREE SURVIVAL; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; NEOPLASM INVASIVENESS; NEOPLASM RECURRENCE, LOCAL; NEOPLASMS, GLANDULAR AND EPITHELIAL; OVARIAN NEOPLASMS; PROTO-ONCOGENE PROTEINS; RECEPTOR TYROSINE KINASE-LIKE ORPHAN RECEPTORS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA INTERFERENCE; WNT PROTEINS; WNT-5A PROTEIN;

EID: 84950115140     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5643     Document Type: Article

References (35)

1. The Cancer Genome Atlas. Integrated genomic analyses of ovarian carcinoma. Nature. 2011; 474:609-615.
2. Tothill RW, Tinker AV, George J, Brown R, Fox SB, Lade S, Johnson DS, Trivett MK, Etemadmoghadam D, Locandro B, Traficante N, Fereday S, Hung JA, Chiew YE, Haviv I Australian Ovarian Cancer Study G, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res. 2008; 14:5198-5208.
3. Tan TZ, Miow QH, Huang RY, Wong MK, Ye J, Lau JA, Wu MC, Bin Abdul Hadi LH, Soong R, Choolani M, Davidson B, Nesland JM, Wang LZ, Matsumura N, Mandai M, Konishi I, et al. Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer. EMBO molecular medicine. 2013; 5:983-998.
4. Loh YN, Hedditch EL, Baker LA, Jary E, Ward RL, Ford CE. The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer. BMC Cancer. 2013; 13:174.
5. Ford CE, Punnia-Moorthy G, Henry CE, Llamosas E, Nixdorf S, Olivier J, Caduff R, Ward RL, Heinzelmann-Schwarz V. The non-canonical Wnt ligand, Wnt5a, is upregulated and associated with epithelial to mesenchymal transition in epithelial ovarian cancer. Gynecologic Oncology. 2014; 134:338-345.
6. Arend RC, Londono-Joshi AI, Straughn JM Jr., Buchsbaum DJ. The Wnt/beta-catenin pathway in ovarian cancer: a review. Gynecologic Oncology. 2013; 131:772-779.
7. Ford CE, Jary E, Ma SS, Nixdorf S, Heinzelmann-Schwarz VA, Ward RL. The Wnt gatekeeper SFRP4 modulates EMT, cell migration and downstream Wnt signalling in serous ovarian cancer cells. PLoS ONE [Electronic Resource]. 2013; 8:e54362.
8. Su HY, Lai HC, Lin YW, Liu CY, Chen CK, Chou YC, Lin SP, Lin WC, Lee HY, Yu MH. Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway. Int J Cancer. 2010;127:555-567.
9. Ford CE, Qian Ma SS, Quadir A, Ward RL. The dual role of the novel Wnt receptor tyrosine kinase, ROR2, in human carcinogenesis. International Journal of Cancer. 2013; 133:779-787.
10. Henry C, Quadir A, Hawkins NJ, Jary E, Llamosas E, Kumar D, Daniels B, Ward RL, Ford CE. Expression of the novel Wnt receptor ROR2 is increased in breast cancer and may regulate both beta-catenin dependent and independent Wnt signalling. J Cancer Res Clin Oncol. 2015; 141:243-254.
11. Lara E, Calvanese V, Huidobro C, Fernandez AF, Moncada-Pazos A, Obaya AJ, Aguilera O, Gonzalez-Sancho JM, Sanchez L, Astudillo A, Munoz A, Lopez-Otin C, Esteller M, Fraga MF. Epigenetic repression of ROR2 has a Wntmediated, pro-tumourigenic role in colon cancer. Mol Cancer. 2010; 9:170.
12. Rasmussen NR, Wright TM, Brooks SA, Hacker KE, Debebe Z, Sendor AB, Walker MP, Major MB, Green J, Wahl GM, Rathmell WK. Receptor tyrosine kinase-like orphan receptor 2 (Ror2) expression creates a poised state of Wnt signaling in renal cancer. Journal of Biological Chemistry. 2013; 288:26301-26310.
13. Sun B, Ye X, Lin L, Shen M, Jiang T. Up-regulation of ROR2 is associated with unfavorable prognosis and tumor progression in cervical cancer. International journal of clinical and experimental pathology. 2015; 8:856-861.
14. Huang J, Fan X, Wang X, Lu Y, Zhu H, Wang W, Zhang S, Wang Z. High ROR2 expression in tumor cells and stroma is correlated with poor prognosis in pancreatic ductal adenocarcinoma. Scientific reports. 2015; 5:12991.
15. Lu C, Wang X, Zhu H, Feng J, Ni S, Huang J. Overexpression of ROR2 and Wnt5a cooperatively correlates with unfavorable prognosis in patients with non-small cell lung cancer. Oncotarget. 2015; 6:24912-24921. doi: 10.18632/oncotarget.4701.
16. Zhang S, Chen L, Cui B, Chuang HY, Yu J, Wang-Rodriguez J, Tang L, Chen G, Basak GW, Kipps TJ. ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PLoS One. 2012; 7:e31127.
17. Cui B, Zhang S, Chen L, Yu J, Widhopf GF, Fecteau JF, Rassenti LZ, Kipps TJ. Targeting ROR1 inhibits epithelialmesenchymal transition and metastasis. Cancer Res. 2013; 73:3649-3660.
18. Zhang H, Qiu J, Ye C, Yang D, Gao L, Su Y, Tang X, Xu N, Zhang D, Xiong L, Mao Y, Li F, Zhu J. ROR1 expression correlated with poor clinical outcome in human ovarian cancer. Scientific reports. 2014; 4:5811.
19. Zhang S, Cui B, Lai H, Liu G, Ghia EM, Widhopf GF 2nd, Zhang Z, Wu CC, Chen L, Wu R, Schwab R, Carson DA, Kipps TJ. Ovarian cancer stem cells express ROR1, which can be targeted for anti-cancer-stem-cell therapy. Proc Natl Acad Sci U S A. 2014; 111:17266-17271.
20. Jacob F, Ukegijni K, Nixdorf S, Ford C, Olivier J, Caduff R, Scurry J, Guertler R, Hornung D, Mueller R, Fink D, Hacker N, Heinzelmann-Schwarz V. Loss of secreted frizzled-related protein 4 correlates with an aggressive phenotype and predicts poor outcome in ovarian cancer patients. PLoS One. 2012; 7:e31885.
21. Rasmussen NR, Debebe Z, Wright TM, Brooks SA, Sendor AB, Brannon AR, Hakimi AA, Hsieh JJ, Choueiri TK, Tamboli P, Maranchie JK, Hinds P, Wallen EM, Simpson C, Norris JL, Janzen WP, et al. Expression of Ror2 mediates invasive phenotypes in renal cell carcinoma. PLoS One. 2014; 9:e116101.
22. Nomachi A, Nishita M, Inaba D, Enomoto M, Hamasaki M, Minami Y. Receptor tyrosine kinase Ror2 mediates Wnt5ainduced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A. J Biol Chem. 2008; 283:27973-27981.
23. He F, Xiong W, Yu X, Espinoza-Lewis R, Liu C, Gu S, Nishita M, Suzuki K, Yamada G, Minami Y, Chen Y. Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development. Development. 2008; 135:3871-3879.
24. Nishita M, Itsukushima S, Nomachi A, Endo M, Wang Z, Inaba D, Qiao S, Takada S, Kikuchi A, Minami Y. Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization. Mol Cell Biol. 2010; 30:3610-3619.
25. Fukuda T, Chen L, Endo T, Tang L, Lu D, Castro JE, Widhopf GF, Rassenti LZ, Cantwell MJ, Prussak CE, Carson DA, Kipps TJ. Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a. Proc Natl Acad Sci U S A. 2008; 105:3047-3052.
26. Karin M. NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harbor perspectives in biology. 2009; 1:a000141.
27. Yamaguchi T, Yanagisawa K, Sugiyama R, Hosono Y, Shimada Y, Arima C, Kato S, Tomida S, Suzuki M, Osada H, Takahashi T. NKX2-1/TITF1/TTF-1-Induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma. Cancer Cell. 2012; 21:348-361.
28. Tseng H-C, Kao H-W, Ho M-R, Chen Y-R, Lin T-W, Lyu P-C, Lin W-C. Cytoskeleton Network and Cellular Migration Modulated by Nuclear-localized Receptor Tyrosine Kinase ROR1. Anticancer research. 2011; 31:4239-4249.
29. Tseng HC, Lyu PC, Lin WC. Nuclear localization of orphan receptor protein kinase (Ror1) is mediated through the juxtamembrane domain. BMC Cell Biol. 2010; 11:48.
30. Choi MY, Widhopf GF 2nd, Wu CC, Cui B, Lao F, Sadarangani A, Cavagnaro J, Prussak C, Carson DA, Jamieson C, Kipps TJ. Pre-clinical Specificity and Safety of UC-961, a First-In-Class Monoclonal Antibody Targeting ROR1. Clinical lymphoma, myeloma & leukemia. 2015; 15:S167-169.
31. Hojjat-Farsangi M, Khan AS, Daneshmanesh AH, Moshfegh A, Sandin A, Mansouri L, Palma M, Lundin J, Osterborg A, Mellstedt H. The tyrosine kinase receptor ROR1 is constitutively phosphorylated in chronic lymphocytic leukemia (CLL) cells. PLoS One. 2013; 8:e78339.
32. Jacob F, Guertler R, Naim S, Nixdorf S, Fedier A, Hacker NF, Heinzelmann-Schwarz V. Careful selection of reference genes is required for reliable performance of RT-qPCR in human normal and cancer cell lines. PloS one. 2013; 8:e59180.
33. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3:RESEARCH004.
34. Geback T, Schulz MM, Koumoutsakos P, Detmar M. TScratch: a novel and simple software tool for automated analysis of monolayer wound healing assays. BioTechniques. 2009; 46:265-274.
35. Therneau T, Grambsch P. Modeling Survival Data: Extending the Cox Model. New York: Springer-Verlag 2000.