pH regulators to target the tumor immune microenvironment in human hepatocellular carcinoma

References

• Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends–an update. Cancer Epidemiol. Biomarkers Prev. 2016;25(1):16–27. doi:10.1158/1055-9965.EPI-15-0578. PMID:26667886
   PubMed Web of Science ®Google Scholar
• Mazzaferro V, Lencioni R, Majno P. Early hepatocellular carcinoma on the procrustean bed of ablation, resection, and transplantation. Semin. Liver Dis. 2014;34(4):415–26. doi:10.1055/s-0034-1394365. PMID:25369303
   PubMed Web of Science ®Google Scholar
• Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: Clinical frontiers and perspectives. Gut. 2014;63(5):844–55. doi:10.1136/gutjnl-2013-306627. PMID:24531850
   PubMed Web of Science ®Google Scholar
• Kudo M. Immune checkpoint inhibition in hepatocellular carcinoma: Basics and ongoing clinical trials. Clinical Trials. Oncology. 2017;92 Suppl 1:50–62. doi:10.1159/000451016.
   Google Scholar
• Pitt JM, Vetizou M, Daillere R, Roberti MP, Yamazaki T, Routy B, Lepage P, Boneca IG, Chamaillard M, Kroemer G, et al. Resistance mechanisms to immune-checkpoint blockade in cancer: Tumor-intrinsic and -extrinsic factors. Immunity. 2016;44(6):1255–69. doi:10.1016/j.immuni.2016.06.001. PMID:27332730
   PubMed Web of Science ®Google Scholar
• Vaupel P, Hockel M, Mayer A. Detection and characterization of tumor hypoxia using pO2 histography. Antioxid. Redox Signal. 2007;9(8):1221–35. doi:10.1089/ars.2007.1628. PMID:17536958
   PubMed Web of Science ®Google Scholar
• Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell. Metab. 2016;23(1):27–47. doi:10.1016/j.cmet.2015.12.006. PMID:26771115
   PubMed Web of Science ®Google Scholar
• Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: A perfect storm for cancer progression. Nat. Rev. Cancer. 2011;11(9):671–7. doi:10.1038/nrc3110. PMID:21833026
   PubMed Web of Science ®Google Scholar
• Ye LY, Chen W, Bai XL, Xu XY, Zhang Q, Xia XF, Sun X, Li GG, Hu QD, Fu QH, et al. Hypoxia-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma induces an immunosuppressive tumor microenvironment to promote metastasis. Cancer Res. 2016;76(4):818–30. doi:10.1158/0008-5472.CAN-15-0977. PMID:26837767
   PubMed Web of Science ®Google Scholar
• Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, Matos C, Bruss C, Klobuch S, Peter K, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell. Metab. 2016;24(5):657–71. doi: S1550-4131(16)30427-2. doi:10.1016/j.cmet.2016.08.011. PMID:27641098
   PubMed Web of Science ®Google Scholar
• Calcinotto A, Filipazzi P, Grioni M, Iero M, De Milito A, Ricupito A, Cova A, Canese R, Jachetti E, Rossetti M, et al. Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes. Cancer Res. 2012;72(11):2746–56. doi:10.1158/0008-5472.CAN-11-1272. PMID:22593198
   PubMed Web of Science ®Google Scholar
• Huber V, Camisaschi C, Berzi A, Ferro S, Lugini L, Triulzi T, Tuccitto A, Tagliabue E, Castelli C, Rivoltini L. Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation. Semin. Cancer Biol. 2017; 43:74–89. Epub 2017/3/6. doi: S1044-579X(17)30036-6. doi:10.1016/j.semcancer.2017.03.001. PMID:28267587
   PubMed Web of Science ®Google Scholar
• Corzo CA, Condamine T, Lu L, Cotter MJ, Youn JI, Cheng P, Cho HI, Celis E, Quiceno DG, Padhya T, et al. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J. Exp. Med. 2010;207(11):2439–53. doi:10.1084/jem.20100587. PMID:20876310
   PubMed Web of Science ®Google Scholar
• Supuran CT. Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov. 2008;7(2):168–81. doi:10.1038/nrd2467. PMID:18167490
   PubMed Web of Science ®Google Scholar
• Fais S, De Milito A, You H, Qin W. Targeting vacuolar H+-ATPases as a new strategy against cancer. Cancer Res. 2007;67(22):10627–30. doi:67/22/10627. doi:10.1158/0008-5472.CAN-07-1805. PMID:18006801
   PubMed Web of Science ®Google Scholar
• Stransky L, Cotter K, Forgac M. The function of V-ATPases in cancer. Physiol. Rev. 2016;96(3):1071–91. doi:10.1152/physrev.00035.2015. PMID:27335445
   PubMed Web of Science ®Google Scholar
• Toei M, Saum R, Forgac M. Regulation and isoform function of the V-ATPases. Biochemistry. 2010;49(23):4715–23. doi:10.1021/bi100397s. PMID:20450191
   PubMed Web of Science ®Google Scholar
• Sun-Wada GH, Wada Y. Role of vacuolar-type proton ATPase in signal transduction. Biochim. Biophys. Acta. 2015;1847(10):1166–72. doi:10.1016/j.bbabio.2015.06.010. PMID:26072192
   PubMed Web of Science ®Google Scholar
• Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat. Rev. Drug Discov. 2011;10(10):767–77. doi:10.1038/nrd3554. PMID:21921921
   PubMed Web of Science ®Google Scholar
• Wilson GK, Tennant DA, McKeating JA. Hypoxia inducible factors in liver disease and hepatocellular carcinoma: Current understanding and future directions. J. Hepatol. 2014;61(6):1397–406. doi:10.1016/j.jhep.2014.08.025. PMID:25157983
   PubMed Web of Science ®Google Scholar
• Wykoff CC, Beasley NJ, Watson PH, Turner KJ, Pastorek J, Sibtain A, Wilson GD, Turley H, Talks KL, Maxwell PH, et al. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res. 2000;60(24):7075–83. PMID:11156414
   PubMed Web of Science ®Google Scholar
• Huang WJ, Jeng YM, Lai HS, Fong IU, Sheu FY, Lai PL, Yuan RH. Expression of hypoxic marker carbonic anhydrase IX predicts poor prognosis in resectable hepatocellular carcinoma. PLoS One. 2015;10(3):e0119181. doi:10.1371/journal.pone.0119181. PMID:25738958
   PubMed Web of Science ®Google Scholar
• Parkkila S, Parkkila AK, Saarnio J, Kivela J, Karttunen TJ, Kaunisto K, Waheed A, Sly WS, Tureci O, Virtanen I, et al. Expression of the membrane-associated carbonic anhydrase isozyme XII in the human kidney and renal tumors. J. Histochem. Cytochem. 2000;48(12):1601–08. doi:10.1177/002215540004801203. PMID:11101628
   PubMed Web of Science ®Google Scholar
• Yamada S, Okumura N, Wei L, Fuchs BC, Fujii T, Sugimoto H, Nomoto S, Takeda S, Tanabe KK, Kodera Y. Epithelial to mesenchymal transition is associated with shorter disease-free survival in hepatocellular carcinoma. Ann. Surg. Oncol. 2014;21(12):3882–90. doi:10.1245/s10434-014-3779-2. PMID:24833103
   PubMed Web of Science ®Google Scholar
• Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, Jia H, Ye Q, Qin LX, Wauthier E, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009;136(3):1012–24. doi:10.1053/j.gastro.2008.12.004. PMID:19150350
   PubMed Web of Science ®Google Scholar
• Winum JY, Carta F, Ward C, Mullen P, Harrison D, Langdon SP, Cecchi A, Scozzafava A, Kunkler I, Supuran CT. Ureido-substituted sulfamates show potent carbonic anhydrase IX inhibitory and antiproliferative activities against breast cancer cell lines. Bioorg. Med. Chem. Lett. 2012;22(14):4681–85. doi:10.1016/j.bmcl.2012.05.083. PMID:22721713
   PubMed Web of Science ®Google Scholar
• Gieling RG, Babur M, Mamnani L, Burrows N, Telfer BA, Carta F, Winum JY, Scozzafava A, Supuran CT, Williams KJ. Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast carcinoma xenografts. J. Med. Chem. 2012;55(11):5591–600. doi:10.1021/jm300529u. PMID:22621623
   PubMed Web of Science ®Google Scholar
• D'Ascenzio M, Carradori S, Secci D, Vullo D, Ceruso M, Akdemir A, Supuran CT. Selective inhibition of human carbonic anhydrases by novel amide derivatives of probenecid: synthesis, biological evaluation and molecular modelling studies. Bioorg. Med. Chem. 2014;22(15):3982–88. doi:10.1016/j.bmc.2014.06.003. PMID:25027802
   PubMed Web of Science ®Google Scholar
• Parks SK, Chiche J, Pouyssegur J. Disrupting proton dynamics and energy metabolism for cancer therapy. Nat. Rev. Cancer. 2013;13(9):611–23. doi:10.1038/nrc3579 PMID:23969692
   PubMed Web of Science ®Google Scholar
• Suzuki M, Suzuki H, Hibi T. Proton pump inhibitors and gastritis. J. Clin. Biochem. Nutr. 2008;42(2):71–75. doi:10.3164/jcbn.2008012. PMID:18385822
   PubMed Web of Science ®Google Scholar
• Fornari F, Pollutri D, Patrizi C, La Bella T, Marinelli S, Casadei Gardini A, Marisi G, Baron Toaldo M, Baglioni M, et al. In Hepatocellular Carcinoma miR-221 Modulates Sorafenib Resistance through Inhibition of Caspase-3-Mediated Apoptosis. Clin. Cancer Res. 2017;23(14):3953–3965. Epub 2017/1/17. doi:10.1158/1078-0432.CCR-16-1464. PMID:28096271
   PubMed Web of Science ®Google Scholar
• Breunig C, Mueller BJ, Umansky L, Wahl K, Hoffmann K, Lehner F, Manns MP, Bantel H, Falk CS. BRaf and MEK inhibitors differentially regulate cell fate and microenvironment in human hepatocellular carcinoma. Clin. Cancer Res. 2014;20(9):2410–23. doi:10.1158/1078-0432.CCR-13-1635. PMID:24573550
   PubMed Web of Science ®Google Scholar
• Cao Z, Fan-Minogue H, Bellovin DI, Yevtodiyenko A, Arzeno J, Yang Q, Gambhir SS, Felsher DW. MYC phosphorylation, activation, and tumorigenic potential in hepatocellular carcinoma are regulated by HMG-CoA reductase. Cancer Res. 2011;71(6):2286–97. doi:10.1158/0008-5472.CAN-10-3367. PMID:21262914
   PubMed Web of Science ®Google Scholar
• Smith AP, Verrecchia A, Faga G, Doni M, Perna D, Martinato F, Guccione E, Amati B. A positive role for Myc in TGFbeta-induced Snail transcription and epithelial-to-mesenchymal transition. Oncogene. 2009;28(3):422–30. doi:10.1038/onc.2008.395. PMID:18978814
   PubMed Web of Science ®Google Scholar
• Sun Y, Shi Z, Lian H, Cai P. Energy metabolic dysfunction as a carcinogenic factor in cancer cells. Clin. Transl. Med. 2016;5(1):14-016-0094-5. Epub 2016 Apr 6. doi:10.1186/s40169-016-0094-5.
   Google Scholar
• Lim S, Phillips JB, Madeira da Silva L, Zhou M, Fodstad O, Owen LB, Tan M. Interplay between Immune Checkpoint Proteins and Cellular Metabolism. Cancer Res. 2017;77(6):1245–49. doi:10.1158/0008-5472.CAN-16-1647. PMID:28246276
   PubMed Web of Science ®Google Scholar
• Lou Y, McDonald PC, Oloumi A, Chia S, Ostlund C, Ahmadi A, Kyle A, Auf dem Keller U, Leung S, Huntsman D, et al. Targeting tumor hypoxia: Suppression of breast tumor growth and metastasis by novel carbonic anhydrase IX inhibitors. Cancer Res. 2011;71(9):3364–76. doi:10.1158/0008-5472.CAN-10-4261. PMID:21415165
   PubMed Web of Science ®Google Scholar
• Gondi G, Mysliwietz J, Hulikova A, Jen JP, Swietach P, Kremmer E, Zeidler R. Antitumor efficacy of a monoclonal antibody that inhibits the activity of cancer-associated carbonic anhydrase XII. Cancer Res. 2013;73(21):6494–503. doi:10.1158/0008-5472.CAN-13-1110. PMID:24030978
   PubMed Web of Science ®Google Scholar
• De Milito A, Canese R, Marino ML, Borghi M, Iero M, Villa A, Venturi G, Lozupone F, Iessi E, Logozzi M, et al. pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity. Int. J. Cancer. 2010;127(1):207–19. doi:10.1002/ijc.25009. PMID:19876915
   PubMed Web of Science ®Google Scholar
• Currie MJ, Beardsley BE, Harris GC, Gunningham SP, Dachs GU, Dijkstra B, Morrin HR, Wells JE, Robinson BA. Immunohistochemical analysis of cancer stem cell markers in invasive breast carcinoma and associated ductal carcinoma in situ: relationships with markers of tumor hypoxia and microvascularity. Hum. Pathol. 2013;44(3):402–11. doi:10.1016/j.humpath.2012.06.004. PMID:23036368
   PubMed Web of Science ®Google Scholar
• Lock FE, McDonald PC, Lou Y, Serrano I, Chafe SC, Ostlund C, Aparicio S, Winum JY, Supuran CT, Dedhar S. Targeting carbonic anhydrase IX depletes breast cancer stem cells within the hypoxic niche. Oncogene. 2013;32(44):5210–19. doi:10.1038/onc.2012.550. PMID:23208505
   PubMed Web of Science ®Google Scholar
• Hjelmeland AB, Wu Q, Heddleston JM, Choudhary GS, MacSwords J, Lathia JD, McLendon R, Lindner D, Sloan A, Rich JN. Acidic stress promotes a glioma stem cell phenotype. Cell Death Differ. 2011;18(5):829–40. doi:10.1038/cdd.2010.150. PMID:21127501
   PubMed Web of Science ®Google Scholar
• van Kuijk SJ, Yaromina A, Houben R, Niemans R, Lambin P, Dubois LJ. Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis. Front. Oncol. 2016;6:69. doi:10.3389/fonc.2016.00069. PMID:27066453
   PubMed Web of Science ®Google Scholar
• Venables JP. Aberrant and alternative splicing in cancer. Cancer Res. 2004;64(21):7647–54. doi:64/21/7647. doi:10.1158/0008-5472.CAN-04-1910. PMID:15520162
   PubMed Web of Science ®Google Scholar
• Oliveira-Ferrer L, Legler K, Milde-Langosch K. Role of protein glycosylation in cancer metastasis. Semin. Cancer Biol. 2017;44:141–152. Epub 2017/3/16. doi:S1044-579X(17)30040-8. doi:10.1016/j.semcancer.2017.03.002. PMID:28673608
   PubMed Web of Science ®Google Scholar
• Marschall AL, Dubel S. Antibodies inside of a cell can change its outside: Can intrabodies provide a new therapeutic paradigm? Comput. Struct. Biotechnol. J. 2016;14:304–8. doi:10.1016/j.csbj.2016.07.003.
   PubMed Web of Science ®Google Scholar
• Taylor S, Spugnini EP, Assaraf YG, Azzarito T, Rauch C, Fais S. (2015) Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach. Drug Resist Updat. 2015;23:69–78. doi:10.1016/j.drup.2015.08.004. PMID:26341193
   PubMed Web of Science ®Google Scholar
• Niikura K. Vacuolar ATPase as a drug discovery target. Drug News. Perspect. 2006;19(3):139–44. doi:977442. doi:10.1358/dnp.2006.19.3.977442. PMID:16804565
   PubMedGoogle Scholar
• Ferrari S, Perut F, Fagioli F, Brach Del Prever A, Meazza C, Parafioriti A, Picci P, Gambarotti M, Avnet S, Baldini N, et al. Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients' bed. J. Transl. Med. 2013;11:268-5876-11-268. doi:10.1186/1479-5876-11-268.
   Web of Science ®Google Scholar
• Toro EJ, Ostrov DA, Wronski TJ, Holliday LS. Rational identification of enoxacin as a novel V-ATPase-directed osteoclast inhibitor. Curr. Protein Pept. Sci. 2012;13(2):180–91. doi:BSP/CPPS/E-Pub/174. doi:10.2174/138920312800493151. PMID:22044158
   PubMed Web of Science ®Google Scholar
• Wang SP, Krits I, Bai S, Lee BS. Regulation of enhanced vacuolar H+-ATPase expression in macrophages. Biol. Chem. 2002;277(11):8827–34. doi:10.1074/jbc.M111959200.
   Web of Science ®Google Scholar
• Fan QM, Jing YY, Yu GF, Kou XR, Ye F, Gao L, Li R, Zhao QD, Yang Y, Lu ZH, et al. Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Lett. 2014;352(2):160–8. doi:10.1016/j.canlet.2014.05.008. PMID:24892648
   PubMed Web of Science ®Google Scholar
• Yeung OW, Lo CM, Ling CC, Qi X, Geng W, Li CX, Ng KT, Forbes SJ, Guan XY, Poon RT, et al. Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma. J. Hepatol. 2015;62(3):607–16. doi:10.1016/j.jhep.2014.10.029. PMID:25450711
   PubMed Web of Science ®Google Scholar
• Chao M, Wu H, Jin K, Li B, Wu J, Zhang G, Yang G, Hu X. A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis. Elife 2016: e15691. doi:10.7554/eLife.15691. doi:10.7554/eLife.15691.
   Google Scholar
• Pilon-Thomas S, Kodumudi KN, El-Kenawi AE, Russell S, Weber AM, Luddy K, Damaghi M, Wojtkowiak JW, Mule JJ, Ibrahim-Hashim A, et al. Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy. Cancer Res. 2016;76(6):1381–90. doi:10.1158/0008-5472.CAN-15-1743 PMID:26719539
   PubMed Web of Science ®Google Scholar
• Gebhardt C, Sevko A, Jiang H, Lichtenberger R, Reith M, Tarnanidis K, Holland-Letz T, Umansky L, Beckhove P, Sucker A, et al. Myeloid Cells and Related Chronic Inflammatory Factors as Novel Predictive Markers in Melanoma Treatment with Ipilimumab. Clin. Cancer Res. 2015;21(24):5453–59. doi:10.1158/1078-0432.CCR-15-0676. PMID:26289067
   PubMed Web of Science ®Google Scholar
• Antonios JP, Soto H, Everson RG, Moughon D, Orpilla JR, Shin NP, Sedighim S, Treger J, Odesa S, Tucker A, et al. Immunosuppressive tumor-infiltrating myeloid cells mediate adaptive immune resistance via a PD-1/PD-L1 mechanism in glioblastoma. Neuro Oncol. 2017;19(6):796–807. doi:10.1093/neuonc/now287. PMID:28115578
   PubMed Web of Science ®Google Scholar