Login Register Cart 0
Generic placeholder image

当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Research Article

具有神经元标记物过度表达的癌症干细胞增强视网膜母细胞瘤的化学抗性和侵袭能力。

卷 20, 期 9, 2020

页: [710 - 719] 页: 10

弟呕挨: 10.2174/1568009620666200504112711

价格: $65

摘要

背景：视网膜母细胞瘤是儿童的一种视力威胁生命的胚胎肿瘤。尽管化学疗法是主要的治疗方式，但耐药性的发展仍然是治疗成功的主要障碍。癌症干细胞（CSC）的存在经常被报道与多种肿瘤的化学耐药有关。 目的：我们的研究旨在确定促进视网膜母细胞瘤中癌症干细胞化学耐药性的分子因素。 方法：我们通过逐步药物增量处理开发了依托泊苷和卡铂耐药性成视网膜细胞瘤（Y79）细胞系，并经MTT和TUNEL分析验证。通过软琼脂菌落形成和transwell分析分别研究了菌落形成和侵袭能力。通过组织病理学对非反应性视网膜母细胞瘤肿瘤进行了类似的分析。最后，通过定量PCR检查CSC /神经元标志物和ABC转运蛋白的表达，并通过Western印迹证实神经元干细胞标志物的蛋白表达。 结果：在软琼脂分析中，耐药细胞的菌落较大，为自我更新能力增强提供了证据。非反应性肿瘤的组织病理学主要显示分化差的细胞。此外，耐药细胞系和非反应性肿瘤均显示出侵袭增加，神经元干细胞标志物SOX2，NANOG，OCT4和ABC转运蛋白ABCB1和ABCC3的表达更高。自我更新能力的增强和侵袭以及抗性细胞和肿瘤中干标记的过度表达为视网膜母细胞瘤中干驱动化学抗性和侵袭提供了证据。 结论：我们已经证明了神经元干细胞/ CSC标记物可以促进癌症干细胞的维持。针对这些因素的开发疗法将有助于克服耐药性并改善视网膜母细胞瘤的治疗。

关键词: 化学抗性，ABC转运蛋白，成视网膜细胞瘤，组织病理学，癌症干细胞，神经元干细胞标志物。

« Previous Next »
图形摘要

[1]
Villegas, V.M.; Hess, D.J.; Wildner, A.; Gold, A.S.; Murray, T.G. Retinoblastoma. Curr. Opin. Ophthalmol., 2013, 24(6), 581-588.
[http://dx.doi.org/10.1097/ICU.0000000000000002] [PMID: 24100372]
[2]
Thirumalairaj, K.; Abraham, A.; Devarajan, B.; Gaikwad, N.; Kim, U.; Muthukkaruppan, V.; Vanniarajan, A. A stepwise strategy for rapid and cost-effective RB1 screening in Indian retinoblastoma patients. J. Hum. Genet., 2015, 60(9), 547-552.
[http://dx.doi.org/10.1038/jhg.2015.62] [PMID: 26084579]
[3]
Meel, R.; Radhakrishnan, V.; Bakhshi, S. Current therapy and recent advances in the management of retinoblastoma. Indian J. Med. Paediatr. Oncol., 2012, 33(2), 80-88.
[http://dx.doi.org/10.4103/0971-5851.99731] [PMID: 22988349]
[4]
Chan, H.S.L.; Thorner, P.S.; Haddad, G.; Gallie, B.L. Multidrug-resistant phenotype in retinoblastoma correlates with P-glycoprotein expression. Ophthalmology, 1991, 98(9), 1425-1431.
[http://dx.doi.org/10.1016/S0161-6420(91)32134-1] [PMID: 1682862]
[5]
Chan, H.S.; Lu, Y.; Grogan, T.M.; Haddad, G.; Hipfner, D.R.; Cole, S.P.; Deeley, R.G.; Ling, V.; Gallie, B.L. Multidrug resistance protein (MRP) expression in retinoblastoma correlates with the rare failure of chemotherapy despite cyclosporine for reversal of P-glycoprotein. Cancer Res., 1997, 57(12), 2325-2330.
[PMID: 9192801]
[6]
Jiang, Z.S.; Sun, Y.Z.; Wang, S.M.; Ruan, J.S. Epithelial-mesenchymal transition: potential regulator of ABC transporters in tumor progression. J. Cancer, 2017, 8(12), 2319-2327.
[http://dx.doi.org/10.7150/jca.19079] [PMID: 28819436]
[7]
Masui, S.; Nakatake, Y.; Toyooka, Y.; Shimosato, D.; Yagi, R.; Takahashi, K.; Okochi, H.; Okuda, A.; Matoba, R.; Sharov, A.A.; Ko, M.S.; Niwa, H. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat. Cell Biol., 2007, 9(6), 625-635.
[http://dx.doi.org/10.1038/ncb1589] [PMID: 17515932]
[8]
Jeon, H.M.; Sohn, Y.W.; Oh, S.Y.; Kim, S.H.; Beck, S.; Kim, S.; Kim, H. ID4 imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9*-mediated suppression of SOX2. Cancer Res., 2011, 71(9), 3410-3421.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-3340] [PMID: 21531766]
[9]
Lee, S.H.; Oh, S.Y.; Do, S.I.; Lee, H.J.; Kang, H.J.; Rho, Y.S.; Bae, W.J.; Lim, Y.C. SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma. Br. J. Cancer, 2014, 111(11), 2122-2130.
[http://dx.doi.org/10.1038/bjc.2014.528] [PMID: 25321191]
[10]
Ben-Porath, I.; Thomson, M.W.; Carey, V.J.; Ge, R.; Bell, G.W.; Regev, A.; Weinberg, R.A. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat. Genet., 2008, 40(5), 499-507.
[http://dx.doi.org/10.1038/ng.127] [PMID: 18443585]
[11]
Seigel, G.M.; Campbell, L.M.; Narayan, M.; Gonzalez-Fernandez, F. Cancer stem cell characteristics in retinoblastoma. Mol. Vis., 2005, 11, 729-737.
[PMID: 16179903]
[12]
Seigel, G.M.; Hackam, A.S.; Ganguly, A.; Mandell, L.M.; Gonzalez-Fernandez, F. Human embryonic and neuronal stem cell markers in retinoblastoma. Mol. Vis., 2007, 13, 823-832.
[PMID: 17615543]
[13]
Shukla, S.; Srivastava, A.; Kumar, S.; Singh, U.; Goswami, S.; Chawla, B.; Bajaj, M.S.; Kashyap, S.; Kaur, J. Expression of multidrug resistance proteins in retinoblastoma. Int. J. Ophthalmol., 2017, 10(11), 1655-1661.
[PMID: 29181307]
[14]
Busch, M.; Philippeit, C.; Weise, A.; Dünker, N. Re-characterization of established human retinoblastoma cell lines. Histochem. Cell Biol., 2015, 143(3), 325-338.
[http://dx.doi.org/10.1007/s00418-014-1285-z] [PMID: 25326674]
[15]
Liu, F. Soft–agar colony formation assay. Bio Protoc., 2012, 2(13) e220
[http://dx.doi.org/10.21769/BioProtoc.220]
[16]
Lee, S.H.; Jeyapalan, J.N.; Appleby, V.; Mohamed Noor, D.A.; Sottile, V.; Scotting, P.J. Dynamic methylation and expression of Oct4 in early neural stem cells. J. Anat., 2010, 217(3), 203-213.
[http://dx.doi.org/10.1111/j.1469-7580.2010.01269.x] [PMID: 20646110]]
[17]
Xu, X.L.; Singh, H.P.; Wang, L.; Qi, D.L.; Poulos, B.K.; Abramson, D.H.; Jhanwar, S.C.; Cobrinik, D. Rb suppresses human cone-precursor-derived retinoblastoma tumours. Nature, 2014, 514(7522), 385-388.
[http://dx.doi.org/10.1038/nature13813] [PMID: 25252974]
[18]
Nair, R.M.; Balla, M.M.; Khan, I.; Kalathur, R.K.R.; Kondaiah, P.; Vemuganti, G.K. In vitro characterization of CD133lo cancer stem cells in Retinoblastoma Y79 cell line. BMC Cancer, 2017, 17(1), 779.
[http://dx.doi.org/10.1186/s12885-017-3750-2] [PMID: 29162051]
[19]
Amaral, M.V.S. DE Sousa Portilho, A.J.; DA Silva, E.L.; DE Oliveira Sales, L.; DA Silva Maués, J.H.; DE Moraes, M.E.A.; Moreira-Nunes, C.A. Establishment of drug-resistant cell lines as a model in experimental oncology: A review. Anticancer Res., 2019, 39(12), 6443-6455.
[http://dx.doi.org/10.21873/anticanres.13858] [PMID: 31810908]
[20]
Kim, C.; Gao, R.; Sei, E.; Brandt, R.; Hartman, J.; Hatschek, T.; Crosetto, N.; Foukakis, T.; Navin, N.E. Chemoresistance evolution in triple-negative breast cancer delineated by single-cell sequencing. Cell, 2018, 173(4), 879-893.
[http://dx.doi.org/10.1016/j.cell.2018.03.041]
[21]
Wang, P.; Wan, W.W.; Xiong, S.L.; Feng, H.; Wu, N. Cancer stem-like cells can be induced through dedifferentiation under hypoxic conditions in glioma, hepatoma and lung cancer. Cell Death Discov., 2017, 3, 16105.
[http://dx.doi.org/10.1038/cddiscovery.2016.105] [PMID: 28179999]
[22]
Chen, X.; Liao, R.; Li, D.; Sun, J. Induced cancer stem cells generated by radiochemotherapy and their therapeutic implications. Oncotarget, 2017, 8(10), 17301-17312.
[http://dx.doi.org/10.18632/oncotarget.14230] [PMID: 28038467]
[23]
Mukherjee, P.; Gupta, A.; Chattopadhyay, D.; Chatterji, U. Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells. Sci. Rep., 2017, 7(1), 9170.
[http://dx.doi.org/10.1038/s41598-017-08971-2] [PMID: 28835684]
[24]
Oliveira, B.R.; Figueiredo, M.A.; Trindade, G.S.; Marins, L.F. OCT4 mutations in human erythroleukemic cells: Implications for multiple drug resistance (MDR) phenotype. Mol. Cell. Biochem., 2015, 400(1-2), 41-50.
[http://dx.doi.org/10.1007/s11010-014-2260-7] [PMID: 25355160]
[25]
Bourguignon, L.Y.; Peyrollier, K.; Xia, W.; Gilad, E. Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells. J. Biol. Chem., 2008, 283(25), 17635-17651.
[http://dx.doi.org/10.1074/jbc.M800109200] [PMID: 18441325]
[26]
Cho, Y.; Lee, H.W.; Kang, H.G.; Kim, H.Y.; Kim, S.J.; Chun, K.H. Cleaved CD44 intracellular domain supports activation of stemness factors and promotes tumorigenesis of breast cancer. Oncotarget, 2015, 6(11), 8709-8721.
[http://dx.doi.org/10.18632/oncotarget.3325] [PMID: 25909162]
[27]
Fredlund, E.; Ringnér, M.; Maris, J.M.; Påhlman, S. High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma. Proc. Natl. Acad. Sci. USA, 2008, 105(37), 14094-14099.
[http://dx.doi.org/10.1073/pnas.0804455105] [PMID: 18780787]
[28]
Enane, F.O.; Saunthararajah, Y.; Korc, M. Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells. Cell Death Dis., 2018, 9(9), 912.
[http://dx.doi.org/10.1038/s41419-018-0919-9] [PMID: 30190481]
[29]
Jögi, A.; Vaapil, M.; Johansson, M.; Påhlman, S. Cancer cell differentiation heterogeneity and aggressive behavior in solid tumors. Ups. J. Med. Sci., 2012, 117(2), 217-224.
[http://dx.doi.org/10.3109/03009734.2012.659294] [PMID: 22376239]
[30]
Chen, Y.L.; Chen, P.M.; Lin, P.Y.; Hsiau, Y.T.; Chu, P.Y. abcg2 overexpression confers poor outcomes in hepatocellular carcinoma of elderly patients. Anticancer Res., 2016, 36(6), 2983-2988.
[PMID: 27272814]
[31]
Filho, J.P.; Correa, Z.M.; Odashiro, A.N.; Coutinho, A.B.; Martins, M.C.; Erwenne, C.M.; Burnier, M.N., Jr Histopathological features and P-glycoprotein expression in retinoblastoma. Invest. Ophthalmol. Vis. Sci., 2005, 46(10), 3478-3483.
[http://dx.doi.org/10.1167/iovs.04-1290] [PMID: 16186322]
[32]
Frank, N.Y.; Schatton, T.; Frank, M.H. The therapeutic promise of the cancer stem cell concept. J. Clin. Invest., 2010, 120(1), 41-50.
[http://dx.doi.org/10.1172/JCI41004] [PMID: 20051635]
[33]
Tripathy, A.; Thakurela, S.; Sahu, M.K.; Uthanasingh, K.; Behera, M.; Ajay, A.K.; Kumari, R. The molecular connection of histopathological heterogeneity in hepatocellular carcinoma: A role of Wnt and Hedgehog signaling pathways. PLoS One, 2018, 13(12) e0208194
[http://dx.doi.org/10.1371/journal.pone.0208194] [PMID: 30513115]
[34]
Baba, J.; Kioi, M.; Akimoto, K.; Nagashima, Y.; Taguri, M.; Inayama, Y.; Aoki, I.; Ohno, S.; Mitsudo, K.; Tohnai, I. atypical protein kinase c λ/ι expression is associated with malignancy of oral squamous cell carcinoma. Anticancer Res., 2018, 38(11), 6291-6297.
[http://dx.doi.org/10.21873/anticanres.12985] [PMID: 30396949]
[35]
Pereira, M.A.; Ramos, M.; Dias, A.R.; Faraj, S.F.; Cirqueira, C.D.S.; de Mello, E.S.; Zilberstein, B.; Alves, V.A.F.; Ribeiro, U., Jr Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy. Chin. J. Cancer Res., 2018, 30(5), 526-536.

Rights & Permissions Print Cite
Article Metrics
23
2
© 2025 Bentham Science Publishers | Privacy Policy