Targeted therapy on glioma migration and invasion

doi:10.3969/j.issn.1672-6731.2019.11.004

Abstract

Abstract:

Malignant glioma, one of the most lethal malignancies, is the most common primary central nervous system tumor with a dismal prognosis. The major obstacle to cure and recurrence is diffuse invasion, which enables glioma cells to escape complete surgical resection and radiotherapy and chemotherapy. Combined with findings in our lab and related articles, this review comprehensively elaborates the therapies target to glioma invasion and migration and relevant molecular mechanisms.

Key words: Glioma, Neoplasm invasiveness, Cell movement, Molecular targeted therapy, Review

摘要：

恶性胶质瘤是临床最为常见的原发性中枢神经系统肿瘤，属于难治性肿瘤之一，患者多预后不良。具有高度侵袭性的胶质瘤细胞可以逃避手术最大切除，以及同步放射治疗和药物化疗，是导致治疗难以奏效和复发的主要原因。回顾本实验室相关研究结果并结合文献，阐述胶质瘤侵袭迁移的相关分子机制及靶向治疗研究进展。

关键词: 神经胶质瘤, 肿瘤侵润, 细胞运动, 分子靶向治疗, 综述

LI Tao, HAI Long, YANG Xue-jun. Targeted therapy on glioma migration and invasion[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2019, 19(11): 819-825.

李涛, 海龙, 杨学军. 胶质瘤侵袭迁移靶向治疗[J]. 中国现代神经疾病杂志, 2019, 19(11): 819-825.

/ / Recommend / Download Citations

URL: https://journal11.magtechjournal.com/cjcnn/EN/10.3969/j.issn.1672-6731.2019.11.004

https://journal11.magtechjournal.com/cjcnn/EN/Y2019/V19/I11/819

References

[1] Chinese central nervous system glioma diagnosis and treatment guidelines. Guidelines for diagnosis and treatment of glioma of central nervous system in China (2015)[J]. Zhonghua Yi Xue Za Zhi, 2016, 96:485-509.[《中国中枢神经系统胶质瘤诊断和治疗指南》编写组.中国中枢神经系统胶质瘤诊断与治疗指南(2015)[J].中华医学杂志, 2016, 96:485-509.]
[2] Kumar HR, Zhong X, Sandoval JA, Hickey RJ, Malkas LH. Applications of emerging molecular technologies in glioblastoma multiforme[J]. Expert Rev Neurother, 2008, 8:1497-1506.
[3] Steeg PS. Targeting metastasis[J]. Nat Rev Cancer, 2016, 16:201-218.
[4] Pàez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Viñals F, Inoue M, Bergers G, Hanahan D, Casanovas O. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis[J]. Cancer Cell, 2009, 15:220-231.
[5] Zhou B, Gibson-Corley KN, Herndon ME, Sun Y, Gustafson-Wagner E, Teoh-Fitzgerald M, Domann FE, Henry MD, Stipp CS. Integrin α 3β 1 can function to promote spontaneous metastasis and lung colonization of invasive breast carcinoma[J]. Mol Cancer Res, 2014, 12:143-154.
[6] Shibue T, Brooks MW, Weinberg RA. An integrin-linked machinery of cytoskeletal regulation that enables experimental tumor initiation and metastatic colonization[J]. Cancer Cell, 2013, 24:481-498.
[7] Bello L, Francolini M, Marthyn P, Zhang J, Carroll RS, Nikas DC, Strasser JF, Villani R, Cheresh DA, Black PM. Alpha (v) beta3 and alpha (v) beta5 integrin expression in glioma periphery[J]. Neurosurgery, 2001, 49:380-389.
[8] Tentori L, Dorio AS, Muzi A, Lacal PM, Ruffini F, Navarra P, Graziani G. The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma[J]. Oncol Rep, 2008, 19:1039-1043.
[9] Oku N, Tokudome Y, Koike C, Nishikawa N, Mori H, Saiki I, Okada S. Liposomal Arg-Gly-Asp analogs effectively inhibit metastatic B16 melanoma colonization in murine lungs[J]. Life Sci, 1996, 58:2263-2270.
[10] Yamada S, Bu XY, Khankaldyyan V, Gonzales-Gomez I, McComb JG, Laug WE. Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice[J]. Neurosurgery, 2006, 59:1304-1312.
[11] Mason WP. End of the road:confounding results of the CORE trial terminate the arduous journey of cilengitide for glioblastoma[J]. Neuro Oncol, 2015, 17:634-635.
[12] Zagzag D, Miller DC, Chiriboga L, Yee H, Newcomb EW. Green fluorescent protein immunohistochemistry as a novel experimental tool for the detection of glioma cell invasion in vivo[J]. Brain Pathol, 2003, 13:34-37.
[13] Ohnishi T, Matsumura H, Izumoto S, Hiraga S, Hayakawa T. A novel model of glioma cell invasion using organotypic brain slice culture[J]. Cancer Res, 1998, 58:2935-2940.
[14] Matsumura H, Ohnishi T, Kanemura Y, Maruno M, Yoshimine T. Quantitative analysis of glioma cell invasion by confocal laser scanning microscopy in a novel brain slice model[J]. Biochem Biophys Res Commun, 2000, 269:513-520.
[15] Stoppini L, Buchs PA, Muller D. A simple method for organotypic cultures of nervous tissue[J]. J Neurosci Methods, 1991, 37:173-182.
[16] Ren BC, Liu B, Chen C, Liu ZF, Wu QL, Yu SP, Zhang B, Wang LL, Zhao K. Improved models of organotypic brain slice in investigating the migration and invasion of glioma cells[J]. Zhonghua Shen Jing Yi Xue Za Zhi, 2013, 12:217-220.[任炳成,刘彬,陈聪,刘志峰,武俏丽,于圣平,张斌,王垒垒,赵凯.改良的三维脑片培养模型研究脑胶质瘤细胞的迁移及侵袭[J].中华神经医学杂志, 2013, 12:217-220.]
[17] Ren B, Yu S, Chen C, Wang L, Liu Z, Wu Q, Wang L, Zhao K, Yang X. Invasion and anti-invasion research of glioma cells in an improved model of organotypic brain slice culture[J]. Tumori, 2015, 101:390-397.
[18] Huang Y, Tong L, Yi L, Zhang C, Hai L, Li T, Yu S, Wang W, Tao Z, Ma H, Liu P, Xie Y, Yang X. Three-dimensional hydrogel is suitable for targeted investigation of amoeboid migration of glioma cells[J]. Mol Med Rep, 2018, 17:250-256.
[19] Huang YB, Tong LQ, Zhang C, Hang L, Li T, Wang W, Yu SP, Xie Y, Yang XJ. Effect of NSC23766 and Y-27632 on invasion and migration of malignant glioma cells and integrin expression based on 3D hydrogel models[J]. Zhonghua Shen Jing Yi Xue Za Zhi, 2017, 16:665-670.[黄玉宝,童鹿青,张辰,海龙,李涛,王伟,于圣平,谢祎,杨学军. NSC23766、Y-27632对3D水凝胶中胶质瘤细胞侵袭迁移及整合素表达的影响[J].中华神经医学杂志, 2017, 16:665-670.]
[20] Chen J, Ananthanarayanan B, Springer KS, Wolf KJ, Sheyman SM, Tran VD, Kumar S. Suppression of LIM kinase 1 and LIM kinase 2 limits glioblastoma invasion[J]. Cancer Res, 2019.[Epub ahead of print]
[21] Sin WC, Aftab Q, Bechberger JF, Leung JH, Chen H, Naus CC. Astrocytes promote glioma invasion via the gap junction protein connexin43[J]. Oncogene, 2016, 35:1504-1516.
[22] Wu CY, Chen CH, Lin CY, Feng LY, Lin YC, Wei KC, Huang CY, Fang JY, Chen PY. CCL5 of glioma-associated microglia/macrophages regulates glioma migration and invasion via calcium-dependent matrix metalloproteinase-2[J]. Neuro Oncol, 2019.[Epub ahead of print]
[23] Liu ZF, Yang XJ, Liu B, Chen C, Ren BC, Wang LL, Zhao K, Yu SP, Ming HL. Effect of silencing Arp2/3 complex expression on invasion and migration of glioma cells[J]. Zhongguo Shen Jing Jing Shen Ji Bing Za Zhi, 2013, 39:129-134.[刘志峰,杨学军,刘彬,陈聪,任炳成,王垒垒,赵恺,于圣平,明浩朗. Arp2/3复合物表达沉默对胶质瘤细胞侵袭和迁移的影响[J].中国神经精神疾病杂志, 2013, 39:129-134.]
[24] Liu Z, Yang X, Chen C, Liu B, Ren B, Wang L, Zhao K, Yu S, Ming H. Expression of the Arp2/3 complex in human gliomas and its role in the migration and invasion of glioma cells[J]. Oncol Rep, 2013, 30:2127-2136.
[25] Wang L, Zhao K, Ren B, Zhu M, Zhang C, Zhao P, Zhou H, Chen L, Yu S, Yang X. Expression of cortactin in human gliomas and its effect on migration and invasion of glioma cells[J]. Oncol Rep, 2015, 34:1815-1824.
[26] Zhang B, Yang XJ, Yu SP, Ming HL, Chen C, Ren BC, Liu ZF, Liu B. Role of Rac1 in glioma stem cell migration and invasion[J]. Zhonghua She Jing Yi Xue Za Zhi, 2013, 12:221-225.[张斌,杨学军,于圣平,明浩朗,陈聪,任炳成,刘志峰,刘彬. Rac1在脑胶质瘤干细胞迁移和侵袭中的作用[J].中华神经医学杂志, 2013, 12:221-225.]
[27] Zhou H, Yang XJ, Zhao PF, Zhang C, Chen L, Zhu M, Yu SP, Zhou XC, Hai L. Silencing expression of LIM kinase 1 inhibits invasion and migration of human glioma cells in vitro[J]. Zhonghua Shen Jing Yi Xue Za Zhi, 2015, 14:541-546.[周华,杨学军,赵鹏飞,张辰,陈磊,朱蒙,于圣平,周星辰,海龙.沉默LIMK1的表达抑制体外胶质瘤细胞的侵袭与迁移[J].中华神经医学杂志, 2015, 14:541-546.]
[28] Chen L, Zhu M, Yu SP, Zhang C, Zhao PF, Zhou H, Hai L, Liu B, Li S. Effect of silencing abelson nonreceptor tyrosine kinases 2 expression on invasion and migration of glioma cells[J]. Zhonghua Shen Jing Yi Xue Za Zhi, 2015, 14:221-226.[陈磊,朱蒙,于圣平,张辰,赵鹏飞,周华,海龙,刘波,李帅. ABL2基因表达沉默对胶质瘤细胞迁移和侵袭的影响[J].中华神经医学杂志, 2015, 14:221-226.]
[29] Riento K, Ridley AJ. Rocks:multifunctional kinases in cell behaviour[J]. Nat Rev Mol Cell Biol, 2003, 4:446-456.
[30] Zhu M, Yang XJ. Role of calcium signaling in neoplasms invasion and migration[J]. Guoji Zhong Liu Xue Za Zhi, 2014, 41:161-164.[朱蒙,杨学军.钙信号在恶性肿瘤侵袭迁移中的作用[J].国际肿瘤学杂志, 2014, 41:161-164.]
[31] Zhu M, Chen L, Zhao P, Zhou H, Zhang C, Yu S, Lin Y, Yang X. Store-operated Ca (2+) entry regulates glioma cell migration and invasion via modulation of Pyk2 phosphorylation[J]. J Exp Clin Cancer Res, 2014, 33:98.
[32] Zhu M, Zhou H, Zhang C, Zhao PF, Chen L, Zhao K, Wang LL, Yu SP, Yang XJ. Role of proline-rich tyrosine kinase 2 on invasion and migration of U251 glioma cell line[J]. Zhonghua Shi Yan Wai Ke Za Zhi, 2015, 32:2050-2053.[朱蒙,周华,张辰,赵鹏飞,陈磊,赵恺,王垒垒,于圣平,杨学军.富含脯氨酸的酪氨酸激酶2在U251胶质瘤细胞侵袭迁移中的作用[J].中华实验外科杂志, 2015, 32:2050-2053.]
[33] Zhao PF, Yang XJ, Zhang C, Chen L, Zhou H, Zhu M, Wang LL, Zhao K, Yu SP, Lin Y, Hai L, Liu B, Zhou XC, Li S. The effects of knockdown of S100A4 on invasion and migration of SNB19 glioma cells[J]. Zhongguo Shen Jing Jing Shen Ji Bing Za Zhi, 2014, 40:746-751.[赵鹏飞,杨学军,张辰,陈磊,周华,朱蒙,王垒垒,赵恺,于圣平,林雨,海龙,刘波,周星辰,李帅.敲低S100A4表达对胶质瘤细胞系SNB19侵袭和迁移的影响[J].中国神经精神疾病杂志, 2014, 40:746-751.]
[34] Li T, Yi L, Hai L, Ma H, Tao Z, Zhang C, Abeysekera IR, Zhao K, Yang Y, Wang W, Liu B, Yu S, Tong L, Liu P, Zhu M, Ren B, Lin Y, Zhang K, Cheng C, Huang Y, Yang X. The interactome and spatial redistribution feature of Ca2+ receptor protein calmodulin reveals a novel role in invadopodia-mediated invasion[J]. Cell Death Dis, 2018, 9:292.
[35] Wang W, Yang XJ. Role of sodium hydrogen exchanger isoform 1 in tumor microenvironment[J]. Guoji Zhong Liu Xue Za Zhi, 2017, 44:205-208.[王伟,杨学军.钠氢交换体1在肿瘤微环境中的作用[J].国际肿瘤学杂志, 2017, 44:205-208.]
[36] Kim Y, Kumar S. CD44-mediated adhesion to hyaluronic acid contributes to mechanosensing and invasive motility[J]. Mol Cancer Res, 2014, 12:1416-1429.
[37] Pietras A, Katz AM, Ekström EJ, Wee B, Halliday JJ, Pitter KL, Werbeck JL, Amankulor NM, Huse JT, Holland EC. Osteopontin-CD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth[J]. Cell Stem Cell, 2014, 14:357-369.
[38] Xie Y, Tong LQ, Li Y, Liu PD, Li JB, Zhang L, Wang XY, Bai Y, Yang XJ. Effect of acidic tumor microenvironment on invasion and migration and its mechanism in glioma cells[J]. Zhonghua Shen Jing Yi Xue Za Zhi, 2019, 18:217-224.[解杨,童鹿青,易立,刘沛东,李佳博,张亮,王旭亚,白宇,杨学军.酸性肿瘤微环境对胶质瘤细胞侵袭迁移能力的影响及其机制研究[J].中华神经医学杂志, 2019, 18:217-224.]
[39] Ma HW, Yu SP, Yang XJ. Na⁺-K⁺-2Cl^- cotransporter 1 and glioma[J]. Guoji Zhong Liu Xue Za Zhi, 2017, 44:926-928.[马海文,于圣平,杨学军.钠钾氯共转运体1与胶质瘤[J].国际肿瘤学杂志, 2017, 44:926-928.]
[40] Ma H, Li T, Tao Z, Hai L, Tong L, Yi L, Abeysekera IR, Liu P, Xie Y, Li J, Yuan F, Zhang C, Yang Y, Ming H, Yu S, Yang X. NKCC1 promotes EMT-like process in GBM via RhoA and Rac1 signaling pathways[J]. J Cell Physiol, 2019, 234:1630-1642.
[41] Rempel SA, Dudas S, Ge S, Gutiérrez JA. Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma[J]. Clin Cancer Res, 2000, 6:102-111.
[42] Chen C, Liu ZF, Ren BC, Liu B, Yu SP, Yang XJ. Distribution of CXCL12 and CXC chemokine receptor-4 in glioblastoma microenviroment and the role of them in invasion and migration[J]. Zhonghua Shi Yan Wai Ke Za Zhi, 2013, 30:1271-1274.[陈聪,刘志峰,任炳成,刘彬,于圣平,杨学军.胶质母细胞瘤微环境中CXCL12/CXC趋化因子受体-4的表达分布及其在肿瘤侵袭迁移中的作用[J].中华实验外科杂志, 2013, 30:1271-1274.]
[43] Zhang B, Yang XJ, Yu SP, Ming HL, Chen C, Ren BC, Liu ZF, Liu B. Role of Rac1 in the SDF-1-induced migration and invasion of human glioma cell line U251[J]. Zhonghua Yi Xue Za Zhi, 2012, 92:727-730.[张斌,杨学军,于圣平,明浩朗,陈聪,任炳成,刘志峰,刘彬. Rac1在基质细胞衍生因子1诱导人脑胶质瘤细胞系U251迁移和侵袭中的作用[J].中华医学杂志, 2012, 92:727-730.]
[44] Liu B, Liu ZF, Ren BC, Chen C, Yu SP, Zhang B, Ming HL, Wang LL, Zhao K. Relationship between Golgi apparatus and cell migration direction in vivo and in vitro[J]. Zhonghua Yi Xue Za Zhi, 2013, 93:2001-2003.[刘彬,刘志峰,任炳成,陈聪,于圣平,张斌,明浩朗,王垒垒,赵恺.高尔基体与细胞运动方向关系的体内外实验研究[J].中华医学杂志, 2013, 93:2001-2003.]
[45] Zhou XC, Hai L, Zhang C, Liu B, Li S, Lin Y, Wang W, Li T, Yang YH, Cheng C, Yu SP, Yang XJ. Effect of Notch1 pathway activation on migration and invasion of glioma stem cells[J]. Zhonghua Shen Jing Yi Xue Za Zhi, 2016, 15:41-46.[周星辰,海龙,张辰,刘波,李帅,林雨,王伟,李涛,杨亦寒,程铖,于圣平,杨学军. Notch1通路活化对胶质瘤干细胞迁移和侵袭能力的影响[J].中华神经医学杂志, 2016, 15:41-46.]
[46] Zhang B, Sun J, Yu SP, Chen C, Liu B, Liu ZF, Ren BC, Ming HL, Yang XJ. Rac1+cells distributed in accordance with CD 133+cells in glioblastomas and the elevated invasiveness of CD 133+glioma cells with higher Rac1 activity[J]. Chin Med J (Engl), 2012, 125:4344-4348.
[47] Zhang C, Hai L, Zhu M, Yu S, Li T, Lin Y, Liu B, Zhou X, Chen L, Zhao P, Zhou H, Huang Y, Zhang K, Ren B, Yang X. Actin cytoskeleton regulator Arp2/3 complex is required for DLL1 activating Notch1 signaling to maintain the stem cell phenotype of glioma initiating cells[J]. Oncotarget, 2017, 8:33353-33364.
[48] Yi L, Zhou X, Li T, Liu P, Hai L, Tong L, Ma H, Tao Z, Xie Y, Zhang C, Yu S, Yang X. Notch1 signaling pathway promotes invasion, self-renewal and growth of glioma initiating cells via modulating chemokine system CXCL12/CXCR4[J]. J Exp Clin Cancer Res, 2019, 38:339.
[49] Peruzzi P, Chiocca EA. Understanding glioma invasion:a necessity for effective therapy[J]. World Neurosurg, 2013, 80(3/4):281-283.
[50] Giese A, Bjerkvig R, Berens ME, Westphal M. Cost of migration:invasion of malignant gliomas and implications for treatment[J]. J Clin Oncol, 2003, 21:1624-1636.
[51] Godlewski J, Nowicki MO, Bronisz A, Nuovo G, Palatini J, De Lay M, Van Brocklyn J, Ostrowski MC, Chiocca EA, Lawler SE. MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells[J]. Mol Cell, 2010, 37:620-632.
[52] Zhao K, Wang L, Li T, Zhu M, Zhang C, Chen L, Zhao P, Zhou H, Yu S, Yang X. The role of miR-451 in the switching between proliferation and migration in malignant glioma cells:AMPK signaling, mTOR modulation and Rac1 activation required[J]. Int J Oncol, 2017, 50:1989-1999.
[53] Zhao K, Wang LL, Zhu M, Yu SP, Zhao PF, Zhou H, Zhang C, Chen L, Ming HL, Yang XJ. The effect and mechanism of miR-451 on migration of glioma cell line U251[J]. Zhonghua Shen Jing Wai Ke Za Zhi, 2014, 30:468-472.[赵恺,王垒垒,朱蒙,于圣平,赵鹏飞,周华,张辰,陈磊,明浩朗,杨学军. miR-451对U251细胞迁移运动能力的影响及其潜在机制[J].中华神经外科杂志, 2014, 30:468-472.]
[54] Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. Structural and functional features of central nervous system lymphatic vessels[J]. Nature, 2015, 523:337-341.
[55] Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC. Chromosomal instability drives metastasis through a cytosolic DNA response[J]. Nature, 2018, 553:467-472.

Please choose a citation manager

Content to export