ROR1-A novel biomarker for chemoresistance in ovarian cancer

Conference item

Shafat, E., Hills, F. and Stordal, B. 2018. ROR1-A novel biomarker for chemoresistance in ovarian cancer. Research Degrees Students' Summer Conference. Middlesex University, London, UK 04 Sep 2018
TitleROR1-A novel biomarker for chemoresistance in ovarian cancer
AuthorsShafat, E., Hills, F. and Stordal, B.
Abstract

Background: Ovarian cancer has one of the highest mortality rates among female reproductive system related cancers. The standard treatment involves cytoreductive surgery followed by chemotherapy. Carboplatin, a platinum-based DNA damaging agent, is the chemotherapeutic drug of choice for treatment. However, most patients relapse with a more chemo-resistant form of the disease. Platinum resistance is both multifactorial and complicated. A novel biomarker; ROR1 was identified which can potentially predict platinum resistance or sensitivity. Aim: To understand how the novel biomarker; ROR1 contributes to and mediates platinum resistance in ovarian cancer. Methods: Four cell lines; HEY, SKOV-3, OAW42 and OVCAR-3 were selected and their resistance profiles to cisplatin was determined. A gene expression assay (qPCR) and sandwich ELISA were carried out to investigate expression levels of the ROR1 in response to platinum-based drug treatments for each cell line. Immunocytochemistry was carried out to determine the localization of ROR1. Knockdown experiments were then carried out to study its effects on chemo-resistance. Results: The HEY cell line was the most resistant to cisplatin (p<0.05) and OVCAR-3 cell line was the most sensitive (p<0.005). A strong correlation between chemo-resistance and ROR1 expression was also established (r= 0.99, p= 0.0051). The cisplatin resistant (HEY) cell line displayed the highest ROR1 protein expression while the sensitive (OVCAR-3) cell line had the lowest. Immunocytochemistry also revealed similar patterns with HEY cells showing the highest ROR1 expression. Gene expression assays of drug-treated cells showed decreasing mRNA levels of ROR1. However, in untreated cells OVCAR-3 cells showed a 2.3-foldchange increase in mRNA levels of ROR1. Mesenchymal marker (Vimentin) was also expressed in the HEY cells while there was no expression of the epithelial markers. Knockdown effects of ROR1 and ROR2 in resistant (HEY) and sensitive (OVCAR-3) cell lines will be presented. Conclusion: ROR1 is a promising chemo-resistant biomarker and will be further validated in tissue microarrays.

Sustainable Development Goals3 Good health and well-being
Middlesex University ThemeHealth & Wellbeing
Research GroupBiomarkers for Cancer group
ConferenceResearch Degrees Students' Summer Conference
Publication dates
Print04 Sep 2018
Publication process dates
Deposited25 Jul 2022
Accepted04 Aug 2018
Output statusPublished
LanguageEnglish
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Busschots, S., O'Toole, S., O'Leary, J. and Stordal, B. 2015. Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells. Experimental Cell Research. 336 (1), pp. 1-14. https://doi.org/10.1016/j.yexcr.2014.12.001
The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer
D’Adhemar, C., Spillane, C., Gallagher, M., Bates, M., Costello, K., Barry-O'Crowley, J., Haley, K., Kernan, N., Murphy, C., Smyth, P., O'Byrne, K., Pennington, S., Cooke, A., Ffrench, B., Martin, C., O'Donnell, D., Hennessy, B., Stordal, B., Finn, S., McCann, A., Gleeson, N., D'Arcy, T., Flood, B., O'Neill, L., Sheils, O., O'Toole, S. and O'Leary, J. 2014. The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer. PLoS ONE. 9 (6), pp. 1-15. https://doi.org/10.1371/journal.pone.0100816
OvMark: a user-friendly system for the identification of prognostic biomarkers in publically available ovarian cancer gene expression datasets
Madden, S., Clarke, C., Stordal, B., Carey, M., Broaddus, R., Gallagher, W., Crown, J., Mills, G. and Hennessy, B. 2014. OvMark: a user-friendly system for the identification of prognostic biomarkers in publically available ovarian cancer gene expression datasets. Molecular Cancer. 13 (1), pp. 1-11. https://doi.org/10.1186/1476-4598-13-241
PARP inhibitors as P-glyoprotein substrates
Lawlor, D., Martin, P., Busschots, S., Thery, J., O'Leary, J.J., Hennessy, B.T. and Stordal, B. 2014. PARP inhibitors as P-glyoprotein substrates. Journal of Pharmaceutical Sciences. 103 (6), pp. 1913-1920. https://doi.org/10.1002/jps.23952
Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells
Doherty, B., Lawlor, D., Gillet, J., Gottesman, M., O'Leary, J. and Stordal, B. 2014. Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells. Anticancer Research. 34 (1), pp. 503-507.
In vitro development of chemotherapy and targeted therapy drug-resistant cancer cell lines: a practical guide with case studies
McDermott, M., Eustace, A., Busschots, S., Breen, L., Crown, J., Clynes, M., O'Donovan, N. and Stordal, B. 2014. In vitro development of chemotherapy and targeted therapy drug-resistant cancer cell lines: a practical guide with case studies. Frontiers in Oncology. 4, pp. 1-16. https://doi.org/10.3389/fonc.2014.00040
Placental syndecan-1 and sulphated glycosaminoglycans are decreased in preeclampsia
Heyer-Chauhan, N., Ovbude, I., Hills, A., Sullivan, M. and Hills, F. 2013. Placental syndecan-1 and sulphated glycosaminoglycans are decreased in preeclampsia. Journal of Perinatal Medicine. https://doi.org/10.1515/jpm-2013-0097
IGFBP-1 in the placenta, membranes and fetal circulation: levels at term and preterm delivery
Hills, F., Gunn, L., Hardiman, P., Thanaratnam, S. and Chard, T. 1996. IGFBP-1 in the placenta, membranes and fetal circulation: levels at term and preterm delivery. Early Human Development. 44 (1), pp. 71-76.
Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy
Hills, F., Iles, R. and Sullivan, M. 2013. Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy. Journal of Perinatal Medicine. 41 (3), pp. 241-249. https://doi.org/10.1515/jpm-2012-0086
BRCA1/2 mutation analysis in 41 ovarian cell lines reveals only one functionally deleterious BRCA1 mutation
Stordal, B., Timms, K., Farrelly, A., Gallagher, D., Busschots, S., Renaud, M., Thery, J., Williams, D., Potter, J., Tran, T., Korpanty, G., Cremona, M., Carey, M., Li, J., Li, Y., Aslan, O., O'Leary, J., Mills, G. and Hennessy, B. 2013. BRCA1/2 mutation analysis in 41 ovarian cell lines reveals only one functionally deleterious BRCA1 mutation. Molecular Oncology. 7 (3), pp. 567-79. https://doi.org/10.1016/j.molonc.2012.12.007
Insulin-like growth factor-II and heparin are anti-apoptotic survival factors in human villous cytotrophoblast
Hills, F., Mehmet, H. and Sullivan, M. 2012. Insulin-like growth factor-II and heparin are anti-apoptotic survival factors in human villous cytotrophoblast. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 163 (1), pp. 11-16. https://doi.org/10.1016/j.ejogrb.2012.03.013
Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein
Stordal, B., Hamon, M., McEneaney, V., Roche, S., Gillet, J., O'Leary, J., Gottesman, M. and Clynes, M. 2012. Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein. PLoS ONE. 7 (7), pp. 1-13. https://doi.org/10.1371/journal.pone.0040717
Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review
Murphy, M. and Stordal, B. 2011. Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review. Drug Resistance Updates. 14 (3), pp. 177-190. https://doi.org/10.1016/j.drup.2011.02.004
Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells
Egan, K., Crowley, D., Smyth, P., O'Toole, S., Spillane, C., Martin, C., Gallagher, M., Canney, A., Norris, L., Conlon, N., McEvoy, L., Ffrench, B., Stordal, B., Keegan, H., Finn, S., McEneaney, V., Laios, A., Ducrée, J., Dunne, E., Smith, L., Berndt, M., Sheils, O., Kenny, D. and O'Leary, J. 2011. Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells. PLoS ONE. 6 (10). https://doi.org/10.1371/journal.pone.0026125
Superovulation, IGFBP-1 and birth weight.
Johnson, M., Irvine, R., Hills, F., Bolton, V., Abbas, A., Brooks, A., Allman, A., Chard, T. and Nicolaides, K. 1995. Superovulation, IGFBP-1 and birth weight. European Journal of Obstetrics, Gynaecology and Reproductive Biology. 59 (2), pp. 193-195.
The effects of labor on maternal and fetal levels of insulin-like growth factor binding protein-1
Hills, F., Crawford, R., Harding, S., Farkas, F. and Chard, T. 1994. The effects of labor on maternal and fetal levels of insulin-like growth factor binding protein-1. American Journal of Obstetrics and Gynecology. 171 (5), pp. 1292-1295.
Insulin-related growth factor binding protein-1 levels in ovum donation pregnancies.
Brooks, A., Johnson, M., Hills, F., Chard, T., Irvine, R. and Abdalla, H. 1995. Insulin-related growth factor binding protein-1 levels in ovum donation pregnancies. European Journal of Obstetrics, Gynaecology and Reproductive Biology. 59 (1), pp. 91-94.
Elevated levels of insulin-like growth factor binding protein-1 in fetal distress.
Crawford, R., Hills, F., Farkas, A. and Chard, T. 1995. Elevated levels of insulin-like growth factor binding protein-1 in fetal distress. British Journal of Obstetrics and Gynaecology. 102 (7), pp. 538-540.
Lack of evidence for a circadian rhythm of IGFBP-1 in the mother and fetus during labour.
Harding, S., Mensah, A., Hills, F., Howell, R. and Chard, T. 1995. Lack of evidence for a circadian rhythm of IGFBP-1 in the mother and fetus during labour. British Journal of Obstetrics and Gynaecology. 102 (11), pp. 891-893.
Raised circulating levels of interleukin-6 in women with an intrauterine contraceptive device.
Wolley, J., Saleem, S., Hills, F., Salem, H., El-Nashar, E. and Chard, T. 1996. Raised circulating levels of interleukin-6 in women with an intrauterine contraceptive device. Gynecologic and Obstetric Investigation. 42 (4), pp. 241-243.
Circulating levels of IGF-I and IGF-binding protein-1 throughout pregnancy: relation to birthweight and maternal weight.
Hills, F., English, J. and Chard, T. 1996. Circulating levels of IGF-I and IGF-binding protein-1 throughout pregnancy: relation to birthweight and maternal weight. Journal of Endocrinology. 148 (2), pp. 303-309. https://doi.org/10.1677/joe.0.1480303
Antenatal dexamethasone therapy does not affect circulating concentrations of insulin-like growth factor binding protein-1.
Ogueh, O., Hills, F., Chard, T. and Johnson, M. 1998. Antenatal dexamethasone therapy does not affect circulating concentrations of insulin-like growth factor binding protein-1. Human Reproduction. 13 (6), pp. 1714-1716. https://doi.org/10.1093/humrep/13.6.1714
Effects of co-trimoxazole, erythromycin, amoxycillin, tetracycline and chloroquine on sperm function in vitro
Hargreaves, C., Rogers, S., Hills, F., Rahman, F., Howell, R. and Homa, S. 1998. Effects of co-trimoxazole, erythromycin, amoxycillin, tetracycline and chloroquine on sperm function in vitro. Human Reproduction. 13 (7), pp. 1878-1886.
Reciprocal imprinting of human GRB10 in placental trophoblast and brain: evolutionary conservation of reversed allelic expression
Monk, D., Arnaud, P., Frost, J., Hills, F., Stanier, P., Feil, R. and Moore, G. 2009. Reciprocal imprinting of human GRB10 in placental trophoblast and brain: evolutionary conservation of reversed allelic expression. Human Molecular Genetics. 18 (16), pp. 3066-3074. https://doi.org/10.1093/hmg/ddp248
Heparin prevents programmed cell death in human trophoblast
Hills, F., Abrahams, V., Gonzalez-Timon, B., Francis, J., Cloke, B., Hinkson, L., Rai, R., Regan, L., Mor, G., Sullivan, M., Lam, E. and Brosens, J. 2006. Heparin prevents programmed cell death in human trophoblast. Molecular Human Reproduction. 12 (4), pp. 237-242.
A longitudinal study of maternal plasma insulin-like growth factor binding protein-1 concentrations during normal pregnancy and pregnancies complicated by pre-eclampsia
Anim-Nyame, N., Hills, F., Soorana, S., Steer, P. and Johnson, M. 2000. A longitudinal study of maternal plasma insulin-like growth factor binding protein-1 concentrations during normal pregnancy and pregnancies complicated by pre-eclampsia. Human Reproduction. 15 (10), pp. 2215-2219. https://doi.org/10.1093/humrep/15.10.2215
Interactions between progesterone receptor isoforms in myometrial cells in human labour
Pieber, D., Allport, V., Hills, F., Johnson, M. and Bennett, P. 2001. Interactions between progesterone receptor isoforms in myometrial cells in human labour. Molecular Human Reproduction. 7 (9), pp. 875-879. https://doi.org/10.1093/molehr/7.9.875
Regulated expression of signal transducer and activator of transcription, Stat5, and its enhancement of PRL expression in human endometrial stromal cells in vitro
Mak, I., Brosens, J., Christian, M., Hills, F., Chamley, L., Regan, L. and White, J. 2002. Regulated expression of signal transducer and activator of transcription, Stat5, and its enhancement of PRL expression in human endometrial stromal cells in vitro. Journal of Clinical Endocrinology and Metabolism. 87 (6), pp. 2581-2588. https://doi.org/10.1210/jc.87.6.2581
Progesterone represses interleukin-8 and cyclo-oxygenase-2 in human lower segment fibroblast cells and amnion epithelial cells
Loudon, J., Elliott, C., Hills, F. and Bennett, P. 2003. Progesterone represses interleukin-8 and cyclo-oxygenase-2 in human lower segment fibroblast cells and amnion epithelial cells. Biology of Reproduction. 69 (1), pp. 331-337.
The relationship between insulin and insulin-like growth factor binding protein-1 is modified by pre-eclampsia.
Anim-Nyame, N., Hills, F., Soorana, S., Steer, P. and Johnson, M. 2003. The relationship between insulin and insulin-like growth factor binding protein-1 is modified by pre-eclampsia. Gynecological endocrinology.. 17 (6), pp. 471-476. https://doi.org/10.1080/09513590312331290408
The insulin-like growth factor system in mammalian pregnancy: a workshop report
Carter, A., Hills, F., O'Gorman, D., Robets, C., Soorana, S., Watson, C. and Westwood, M. 2004. The insulin-like growth factor system in mammalian pregnancy: a workshop report. Placenta. 25 (Supple), pp. S53-S56. https://doi.org/10.1016/j.placenta.2004.01.019
Imprinting of IGF2 P0 transcript and novel alternatively spliced INS-IGF2 isoforms show differences between mouse and human
Monk, D., Sanches, R., Arnaud, P., Apostolidou, S., Hills, F., Abu-Amero, S., Murrell, A., Friess, H., Reik, W. and Stanier, P. 2006. Imprinting of IGF2 P0 transcript and novel alternatively spliced INS-IGF2 isoforms show differences between mouse and human. Human Molecular Genetics. 15 (8), pp. 1259-1269. https://doi.org/10.1093/hmg/ddl041
ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair
Stordal, B. and Davey, R. 2009. ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair. Cancer Chemotherapy and Pharmacology. 63 (4), pp. 661-672. https://doi.org/10.1007/s00280-008-0783-x
Citations, citations everywhere but did anyone read the paper? [Letter to the Editor]
Stordal, B. 2009. Citations, citations everywhere but did anyone read the paper? [Letter to the Editor]. Colloids and surfaces. B, Biointerfaces. 72 (2), pp. 312 -312. https://doi.org/10.1016/j.colsurfb.2009.04.001
A systematic review of genes involved in the inverse resistance relationship between cisplatin and paclitaxel chemotherapy: role of BRCA1
Stordal, B. and Davey, R. 2009. A systematic review of genes involved in the inverse resistance relationship between cisplatin and paclitaxel chemotherapy: role of BRCA1. Current Cancer Drug Targets. 9 (3), pp. 354-365. https://doi.org/10.2174/156800909788166592
STOX1 is not imprinted and is not likely to be involved in preeclampsia.
Hills, F., Iglesias-Platas, I., Jebbink, J. and Monk, D. 2007. STOX1 is not imprinted and is not likely to be involved in preeclampsia. Nature Genetics. 39 (3), pp. 279-280. https://doi.org/10.1038/ng0307-279
Limited evolutionary conservation of imprinting in the human placenta
Hills, F., Apostolidou, S., Arnaud, P. and Monk, D. 2006. Limited evolutionary conservation of imprinting in the human placenta. Proceedings of the National Academy of Sciences. 103 (17), pp. 6623-6628. https://doi.org/10.1073/pnas.0511031103
Platinum resistance needs the mythbusters [Letter to the Editor]
Stordal, B. and Davey, R. 2008. Platinum resistance needs the mythbusters [Letter to the Editor]. Toxicology letters. 180 (3), p. 230. https://doi.org/10.1016/j.toxlet.2008.07.003
A 39 kDa fragment of endogenous ASK1 suggests specific cleavage not degradation by the proteasome
Stordal, B. and Davey, R. 2008. A 39 kDa fragment of endogenous ASK1 suggests specific cleavage not degradation by the proteasome. IUBMB Life. 60 (3), pp. 180-184. https://doi.org/10.1002/iub.24
A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship
Stordal, B., Pavlakis, N. and Davey, R. 2007. A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship. Cancer Treatment Reviews. 33 (8), pp. 688-703. https://doi.org/10.1016/j.ctrv.2007.07.013
Understanding cisplatin resistance using cellular models
Stordal, B. and Davey, M. 2007. Understanding cisplatin resistance using cellular models. IUBMB Life. 59 (11), pp. 696-699. https://doi.org/10.1080/15216540701636287
Oxaliplatin for the treatment of cisplatin-resistant cancer: a systematic review
Stordal, B., Pavlakis, N. and Davey, R. 2007. Oxaliplatin for the treatment of cisplatin-resistant cancer: a systematic review. Cancer Treatment Reviews. 33 (4), pp. 347-357. https://doi.org/10.1016/j.ctrv.2007.01.009
Similar chromosomal changes in cisplatin and oxaliplatin-resistant sublines of the H69 SCLC cell line are not associated with platinum resistance
Stordal, B., Peters, G. and Davey, R. 2006. Similar chromosomal changes in cisplatin and oxaliplatin-resistant sublines of the H69 SCLC cell line are not associated with platinum resistance. Genes, Chromosomes & Cancer. 45 (12), pp. 1094-105. https://doi.org/10.1002/gcc.20373
Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells
Stordal, B., Davey, M. and Davey, R. 2006. Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells. Cancer Chemotherapy and Pharmacology. 58 (2), pp. 256-265. https://doi.org/10.1007/s00280-005-0148-7
Regulation of human villous trophoblast by insulin-like growth factors and insulin-like growth factor-binding protein-1
Hills, F., Chard, T., Elder, M. and Sullivan, M. 2004. Regulation of human villous trophoblast by insulin-like growth factors and insulin-like growth factor-binding protein-1. Journal of Endocrinology. 183 (3), pp. 487-496. https://doi.org/10.1677/joe.1.05867
Polyclonal anti-tumor necrosis factor-alpha Fab used as an ancillary treatment for severe malaria
Looareesuwan, S., Sjorstrom, L., Krudsood, S., Wilairatana, P., Porter, R., Hills, F. and Warrell, D. 1999. Polyclonal anti-tumor necrosis factor-alpha Fab used as an ancillary treatment for severe malaria. The American Journal of Tropical Medicine and Hygiene. 61 (1), pp. 26-33. https://doi.org/10.4269/ajtmh.1999.61.26
Mechanism of action of the intrauterine contraceptive device: evidence for a specific biochemical deficiency in the endometrium
Seleem, S., Hills, F., Salem, H., El-Nashar, E. and Chard, T. 1996. Mechanism of action of the intrauterine contraceptive device: evidence for a specific biochemical deficiency in the endometrium. Human Reproduction. 11 (6), pp. 1220-1222.