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当代肿瘤药物靶点

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

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Research Article

谷氨酰胺酶在头颈癌中的表达及其与临床病理参数的关系

卷 22, 期 2, 2022

发表于: 03 March, 2022

页: [169 - 179] 页: 11

弟呕挨: 10.2174/1568009622666211224111425

价格: $65

摘要

背景：增加的谷氨酰胺代谢是癌细胞的特征。谷氨酰胺和谷氨酸之间的相互转化是由两种谷氨酰胺酶亚型 GLS1 和 GLS2 催化的，它们似乎在不同类型的癌症中具有不同的作用。我们首次研究了 GLS1 和 GLS2 的蛋白质表达，以及它们与头颈癌晚期临床病理参数的相关性。 方法：组织微阵列的连续载玻片由 80 个从正常到转移的样本组成，对 GLS1、GLS2、HIF-1α 或 CD147 进行免疫组织化学染色。在两位病理学专家的分析之后，我们对分数进行了统计分析。 结果：与正常组织相比，发现 GLS1 和 GLS2 在头颈部肿瘤中的蛋白质水平上调，并且这种增加的表达与肿瘤分级呈正相关（GLS1）和负相关（GLS2），表明 GLS 酶之间的表达发生变化基于肿瘤分化的亚型。 GLS1 表达增加与 CD147 高表达相关，GLS2 表达升高与 CD147 和 HIF-1α 高表达相关。 GLS1 和 GLS2 与 HIF-1α 或 CD147 的相关性与更高级的临床病理学参数密切相关。 结论： GLS1 和 GLS2 表达增加可作为治疗头颈癌的新方法进行探索。

关键词: 谷氨酰胺酶、GLS1、GLS2、CD147、免疫组化、头颈癌。

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[1]
Thompson-Harvey, A.; Yetukuri, M.; Hansen, A.R.; Simpson, M.C.; Adjei Boakye, E.; Varvares, M.A.; Osazuwa-Peters, N. Rising incidence of late-stage head and neck cancer in the United States. Cancer, 2020, 126(5), 1090-1101.
[http://dx.doi.org/10.1002/cncr.32583] [PMID: 31722124]
[2]
Guidi, A.; Codecà, C.; Ferrari, D. Chemotherapy and immunotherapy for recurrent and metastatic head and neck cancer: A systematic review. Med. Oncol., 2018, 35(3), 37.
[http://dx.doi.org/10.1007/s12032-018-1096-5] [PMID: 29441454]
[3]
Brands, M.T.; Smeekens, E.A.J.; Takes, R.P.; Kaanders, J.H.A.M.; Verbeek, A.L.M.; Merkx, M.A.W.; Geurts, S.M.E. Time patterns of recurrence and second primary tumors in a large cohort of patients treated for oral cavity cancer. Cancer Med., 2019, 8(12), 5810-5819.
[http://dx.doi.org/10.1002/cam4.2124] [PMID: 31400079]
[4]
Teicher, B.A.; Linehan, W.M.; Helman, L.J. Targeting cancer metabolism. Clin. Cancer Res., 2012, 18(20), 5537-5545.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-2587] [PMID: 23071355]
[5]
Liberti, M.V.; Locasale, J.W. The Warburg effect: How does it benefit cancer cells? Trends Biochem. Sci., 2016, 41(3), 211-218.
[http://dx.doi.org/10.1016/j.tibs.2015.12.001] [PMID: 26778478]
[6]
Curthoys, N.P.; Watford, M. Regulation of glutaminase activity and glutamine metabolism. Annu. Rev. Nutr., 1995, 15, 133-159.
[http://dx.doi.org/10.1146/annurev.nu.15.070195.001025] [PMID: 8527215]
[7]
Aledo, J.C.; Gómez-Fabre, P.M.; Olalla, L.; Márquez, J. Identification of two human glutaminase loci and tissue-specific expression of the two related genes. Mamm. Genome, 2000, 11(12), 1107-1110.
[http://dx.doi.org/10.1007/s003350010190] [PMID: 11130979]
[8]
Xiang, L.; Mou, J.; Shao, B.; Wei, Y.; Liang, H.; Takano, N.; Semenza, G.L.; Xie, G. Glutaminase 1 expression in colorectal cancer cells is induced by hypoxia and required for tumor growth, invasion, and metastatic colonization. Cell Death Dis., 2019, 10(2), 40.
[http://dx.doi.org/10.1038/s41419-018-1291-5] [PMID: 30674873]
[9]
Son, J.; Lyssiotis, C.A.; Ying, H.; Wang, X.; Hua, S.; Ligorio, M.; Perera, R.M.; Ferrone, C.R.; Mullarky, E.; Shyh-Chang, N.; Kang, Y.; Fleming, J.B.; Bardeesy, N.; Asara, J.M.; Haigis, M.C.; DePinho, R.A.; Cantley, L.C.; Kimmelman, A.C. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature, 2013, 496(7443), 101-105.
[http://dx.doi.org/10.1038/nature12040] [PMID: 23535601]
[10]
Ren, L.; Ruiz-Rodado, V.; Dowdy, T.; Huang, S.; Issaq, S.H.; Beck, J.; Wang, H.; Tran Hoang, C.; Lita, A.; Larion, M.; LeBlanc, A.K. Glutaminase-1 (GLS1) inhibition limits metastatic progression in osteosarcoma. Cancer Metab., 2020, 8(1), 4.
[http://dx.doi.org/10.1186/s40170-020-0209-8] [PMID: 32158544]
[11]
Gross, M.I.; Demo, S.D.; Dennison, J.B.; Chen, L.; Chernov-Rogan, T.; Goyal, B.; Janes, J.R.; Laidig, G.J.; Lewis, E.R.; Li, J.; Mackinnon, A.L.; Parlati, F.; Rodriguez, M.L.; Shwonek, P.J.; Sjogren, E.B.; Stanton, T.F.; Wang, T.; Yang, J.; Zhao, F.; Bennett, M.K. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol. Cancer Ther., 2014, 13(4), 890-901.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0870] [PMID: 24523301]
[12]
Shen, Y.A.; Hong, J.; Asaka, R.; Asaka, S.; Hsu, F.C.; Suryo Rahmanto, Y.; Jung, J.G.; Chen, Y.W.; Yen, T.T.; Tomaszewski, A.; Zhang, C.; Attarwala, N.; DeMarzo, A.M.; Davidson, B.; Chuang, C.M.; Chen, X.; Gaillard, S.; Le, A.; Shih, I.M.; Wang, T.L. Inhibition of the MYC-regulated glutaminase metabolic axis is an effective synthetic lethal approach for treating chemoresistant ovarian cancers. Cancer Res., 2020, 80(20), 4514-4526.
[PMID: 32859605]
[13]
Lee, Y.Z.; Yang, C.W.; Chang, H.Y.; Hsu, H.Y.; Chen, I.S.; Chang, H.S.; Lee, C.H.; Lee, J.C.; Kumar, C.R.; Qiu, Y.Q.; Chao, Y.S.; Lee, S.J. Discovery of selective inhibitors of Glutaminase-2, which inhibit mTORC1, activate autophagy and inhibit proliferation in cancer cells. Oncotarget, 2014, 5(15), 6087-6101.
[http://dx.doi.org/10.18632/oncotarget.2173] [PMID: 25026281]
[14]
Koch, K.; Hartmann, R.; Tsiampali, J.; Uhlmann, C.; Nickel, A-C.; He, X.; Kamp, M.A.; Sabel, M.; Barker, R.A.; Steiger, H-J.; Hänggi, D.; Willbold, D.; Maciaczyk, J.; Kahlert, U.D. A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity. Cell Death Discov., 2020, 6(1), 20.
[http://dx.doi.org/10.1038/s41420-020-0258-3] [PMID: 32337072]
[15]
Masoud, G.N.; Li, W. HIF-1α pathway: Role, regulation and intervention for cancer therapy. Acta Pharm. Sin. B, 2015, 5(5), 378-389.
[http://dx.doi.org/10.1016/j.apsb.2015.05.007] [PMID: 26579469]
[16]
Jun, J.C.; Rathore, A.; Younas, H.; Gilkes, D.; Polotsky, V.Y. Hypoxia-inducible factors and cancer. Curr. Sleep Med. Rep., 2017, 3(1), 1-10.
[http://dx.doi.org/10.1007/s40675-017-0062-7] [PMID: 28944164]
[17]
Le, Q-T.; Courter, D. Clinical biomarkers for hypoxia targeting. Cancer Metastasis Rev., 2008, 27(3), 351-362.
[http://dx.doi.org/10.1007/s10555-008-9144-9] [PMID: 18483785]
[18]
Semenza, G.L. HIF-1: upstream and downstream of cancer metabolism. Curr. Opin. Genet. Dev., 2010, 20(1), 51-56.
[http://dx.doi.org/10.1016/j.gde.2009.10.009] [PMID: 19942427]
[19]
Cui, X.G.; Han, Z.T.; He, S.H.; Wu, X.D.; Chen, T.R.; Shao, C.H.; Chen, D.L.; Su, N.; Chen, Y.M.; Wang, T.; Wang, J.; Song, D.W.; Yan, W.J.; Yang, X.H.; Liu, T.; Wei, H.F.; Xiao, J. HIF1/2α mediates hypoxia-induced LDHA expression in human pancreatic cancer cells. Oncotarget, 2017, 8(15), 24840-24852.
[http://dx.doi.org/10.18632/oncotarget.15266] [PMID: 28193910]
[20]
Gabison, E.E.; Hoang-Xuan, T.; Mauviel, A.; Menashi, S. EMMPRIN/CD147, an MMP modulator in cancer, development and tissue repair. Biochimie, 2005, 87(3-4), 361-368.
[http://dx.doi.org/10.1016/j.biochi.2004.09.023] [PMID: 15781323]
[21]
Lian, C.; Guo, Y.; Zhang, J.; Chen, X.; Peng, C. Targeting CD147 is a novel strategy for antitumor therapy. Curr. Pharm. Des., 2017, 23(29), 4410-4421.
[http://dx.doi.org/10.2174/1381612823666170710144759] [PMID: 28699528]
[22]
Landras, A.; Reger de Moura, C.; Jouenne, F.; Lebbe, C.; Menashi, S.; Mourah, S. CD147 is a promising target of tumor progression and a prognostic biomarker. Cancers, 2019, 11(11), E1803.
[http://dx.doi.org/10.3390/cancers11111803] [PMID: 31744072]
[23]
Yu, B.; Zhang, Y.; Wu, K.; Wang, L.; Jiang, Y.; Chen, W.; Yan, M. CD147 promotes progression of head and neck squamous cell carcinoma via NF-kappa B signaling. J. Cell. Mol. Med., 2019, 23(2), 954-966.
[http://dx.doi.org/10.1111/jcmm.13996] [PMID: 30421493]
[24]
Saha, S.K.; Islam, S.M.R.; Abdullah-Al-Wadud, M.; Islam, S.; Ali, F.; Park, K.S. Multiomics analysis reveals that GLS and GLS2 differentially modulate the clinical outcomes of cancer. J. Clin. Med., 2019, 8(3), 355.
[http://dx.doi.org/10.3390/jcm8030355] [PMID: 30871151]
[25]
Li, X.; Zhang, Y.; Ma, W.; Fu, Q.; Liu, J.; Yin, G.; Chen, P.; Dai, D.; Chen, W.; Qi, L.; Yu, X.; Xu, W. Enhanced glucose metabolism mediated by CD147 contributes to immunosuppression in hepatocellular carcinoma. Cancer Immunol. Immunother., 2020, 69(4), 535-548.
[http://dx.doi.org/10.1007/s00262-019-02457-y] [PMID: 31965268]
[26]
Matés, J.M.; Di Paola, F.J.; Campos-Sandoval, J.A.; Mazurek, S.; Márquez, J. Therapeutic targeting of glutaminolysis as an essential strategy to combat cancer. Semin. Cell Dev. Biol., 2020, 98, 34-43.
[http://dx.doi.org/10.1016/j.semcdb.2019.05.012] [PMID: 31100352]
[27]
Swartz, J.E.; Pothen, A.J.; Stegeman, I.; Willems, S.M.; Grolman, W. Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: A systematic review. Cancer Med., 2015, 4(7), 1101-1116.
[http://dx.doi.org/10.1002/cam4.460] [PMID: 25919147]
[28]
Xin, X.; Zeng, X.; Gu, H.; Li, M.; Tan, H.; Jin, Z.; Hua, T.; Shi, R.; Wang, H. CD147/EMMPRIN overexpression and prognosis in cancer: A systematic review and meta-analysis. Sci. Rep., 2016, 6, 32804.
[http://dx.doi.org/10.1038/srep32804] [PMID: 27608940]
[29]
Cluntun, A.A.; Lukey, M.J.; Cerione, R.A.; Locasale, J.W. Glutamine metabolism in cancer: understanding the heterogeneity. Trends Cancer, 2017, 3(3), 169-180.
[http://dx.doi.org/10.1016/j.trecan.2017.01.005] [PMID: 28393116]
[30]
Li, B.; Cao, Y.; Meng, G.; Qian, L.; Xu, T.; Yan, C.; Luo, O.; Wang, S.; Wei, J.; Ding, Y.; Yu, D. Targeting glutaminase 1 attenuates stemness properties in hepatocellular carcinoma by increasing reactive oxygen species and suppressing Wnt/beta-catenin pathway. EBioMedicine, 2019, 39, 239-254.
[http://dx.doi.org/10.1016/j.ebiom.2018.11.063] [PMID: 30555042]
[31]
Kim, J.Y.; Heo, S-H.; Choi, S.K.; Song, I.H.; Park, I.A.; Kim, Y-A.; Park, H.S.; Park, S.Y.; Bang, W.S.; Gong, G.; Lee, H.J. Glutaminase expression is a poor prognostic factor in node-positive triple-negative breast cancer patients with a high level of tumor-infiltrating lymphocytes. Virchows Arch., 2017, 470(4), 381-389.
[http://dx.doi.org/10.1007/s00428-017-2083-5] [PMID: 28185053]
[32]
Huang, F.; Zhang, Q.; Ma, H.; Lv, Q.; Zhang, T. Expression of glutaminase is upregulated in colorectal cancer and of clinical significance. Int. J. Clin. Exp. Pathol., 2014, 7(3), 1093-1100.
[PMID: 24696726]
[33]
Matre, P.; Velez, J.; Jacamo, R.; Qi, Y.; Su, X.; Cai, T.; Chan, S.M.; Lodi, A.; Sweeney, S.R.; Ma, H.; Davis, R.E.; Baran, N.; Haferlach, T.; Su, X.; Flores, E.R.; Gonzalez, D.; Konoplev, S.; Samudio, I.; DiNardo, C.; Majeti, R.; Schimmer, A.D.; Li, W.; Wang, T.; Tiziani, S.; Konopleva, M. Inhibiting glutaminase in acute myeloid leukemia: Metabolic dependency of selected AML subtypes. Oncotarget, 2016, 7(48), 79722-79735.
[http://dx.doi.org/10.18632/oncotarget.12944] [PMID: 27806325]
[34]
Szeliga, M.; Bogacińska-Karaś, M.; Różycka, A.; Hilgier, W.; Marquez, J.; Albrecht, J. Silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the proliferation and viability of glioblastoma cells. Tumour Biol., 2014, 35(3), 1855-1862.
[http://dx.doi.org/10.1007/s13277-013-1247-4] [PMID: 24096582]
[35]
Dias, M.M.; Adamoski, D.; Dos Reis, L.M.; Ascenção, C.F.R.; de Oliveira, K.R.S.; Mafra, A.C.P.; da Silva Bastos, A.C.; Quintero, M.; de G Cassago, C.; Ferreira, I.M.; Fidelis, C.H.V.; Rocco, S.A.; Bajgelman, M.C.; Stine, Z.; Berindan-Neagoe, I.; Calin, G.A.; Ambrosio, A.L.B.; Dias, S.M.G. GLS2 is protumorigenic in breast cancers. Oncogene, 2020, 39(3), 690-702.
[http://dx.doi.org/10.1038/s41388-019-1007-z] [PMID: 31541193]
[36]
Pérez-Gómez, C.; Campos-Sandoval, J.A.; Alonso, F.J.; Segura, J.A.; Manzanares, E.; Ruiz-Sánchez, P.; González, M.E.; Márquez, J.; Matés, J.M. Co-expression of glutaminase K and L isoenzymes in human tumour cells. Biochem. J., 2005, 386(Pt 3), 535-542.
[http://dx.doi.org/10.1042/BJ20040996] [PMID: 15496140]
[37]
Yu, D.; Shi, X.; Meng, G.; Chen, J.; Yan, C.; Jiang, Y.; Wei, J.; Ding, Y. Kidney-type glutaminase (GLS1) is a biomarker for pathologic diagnosis and prognosis of hepatocellular carcinoma. Oncotarget, 2015, 6(10), 7619-7631.
[http://dx.doi.org/10.18632/oncotarget.3196] [PMID: 25844758]
[38]
Yuneva, M.O.; Fan, T.W.; Allen, T.D.; Higashi, R.M.; Ferraris, D.V.; Tsukamoto, T.; Matés, J.M.; Alonso, F.J.; Wang, C.; Seo, Y.; Chen, X.; Bishop, J.M. The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab., 2012, 15(2), 157-170.
[http://dx.doi.org/10.1016/j.cmet.2011.12.015] [PMID: 22326218]
[39]
Kirk, P.; Wilson, M.C.; Heddle, C.; Brown, M.H.; Barclay, A.N.; Halestrap, A.P. CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J., 2000, 19(15), 3896-3904.
[http://dx.doi.org/10.1093/emboj/19.15.3896] [PMID: 10921872]
[40]
Schneiderhan, W.; Scheler, M.; Holzmann, K.H.; Marx, M.; Gschwend, J.E.; Bucholz, M.; Gress, T.M.; Seufferlein, T.; Adler, G.; Oswald, F. CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in vivo and in vitro models. Gut, 2009, 58(10), 1391-1398.
[http://dx.doi.org/10.1136/gut.2009.181412] [PMID: 19505879]
[41]
de la Cruz-López, K.G.; Castro-Muñoz, L.J.; Reyes-Hernández, D.O.; García-Carrancá, A.; Manzo-Merino, J. Lactate in the regulation of tumor microenvironment and therapeutic approaches. Front. Oncol., 2019, 9(1143), 1143.
[http://dx.doi.org/10.3389/fonc.2019.01143] [PMID: 31737570]
[42]
Pérez-Escuredo, J.; Dadhich, R.K.; Dhup, S.; Cacace, A.; Van Hée, V.F.; De Saedeleer, C.J.; Sboarina, M.; Rodriguez, F.; Fontenille, M-J.; Brisson, L.; Porporato, P.E.; Sonveaux, P. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells. Cell Cycle, 2016, 15(1), 72-83.
[http://dx.doi.org/10.1080/15384101.2015.1120930] [PMID: 26636483]
[43]
Jing, X.; Yang, F.; Shao, C.; Wei, K.; Xie, M.; Shen, H.; Shu, Y. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol. Cancer, 2019, 18(1), 157.
[http://dx.doi.org/10.1186/s12943-019-1089-9] [PMID: 31711497]
[44]
Brown, J.M. Tumor hypoxia in cancer therapy.Methods Enzymol., 2007, 435, 295-321.
[45]
Al Tameemi, W.; Dale, T.P.; Al-Jumaily, R.M.K.; Forsyth, N.R. Hypoxia-modified cancer cell metabolism. Front. Cell Dev. Biol., 2019, 7, 4.
[http://dx.doi.org/10.3389/fcell.2019.00004] [PMID: 30761299]
[46]
Lai, S.Y.; Rubin-Grandis, J. HIF-1 modulates head and neck cancer progression and invasion. Otolaryngol. Head Neck Surg., 2004, 131(2), 112.
[http://dx.doi.org/10.1016/j.otohns.2004.06.159]
[47]
Basheer, H.A.; Pakanavicius, E.; Cooper, P.A.; Shnyder, S.D.; Martin, L.; Hunter, K.D.; Vinader, V.; Afarinkia, K. Hypoxia modulates CCR7 expression in head and neck cancers. Oral Oncol., 2018, 80, 64-73.
[http://dx.doi.org/10.1016/j.oraloncology.2018.03.014] [PMID: 29706190]
[48]
Ban, H. S.; Kim, B.-K.; Lee, H.; Kim, H. M.; Harmalkar, D.; Nam, M.; Park, S.-K.; Lee, K.; Park, J.-T.; Kim, I.; Lee, K.; Hwang, G.-S.; Won, M. The novel hypoxia-inducible factor-1α inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth. Cell Death Dis., 2017, 8(6), e2843-e.
[http://dx.doi.org/10.1038/cddis.2017.235]
[49]
Semenza, G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer, 2003, 3(10), 721-732.
[http://dx.doi.org/10.1038/nrc1187] [PMID: 13130303]

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