Tumour acidosis evaluated in vivo by MRI-CEST pH imaging reveals breast cancer metastatic potential.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
18
09
2019
accepted:
28
10
2020
revised:
07
10
2020
pubmed:
2
12
2020
medline:
21
4
2021
entrez:
1
12
2020
Statut:
ppublish
Résumé
Tumour acidosis is considered to play a central role in promoting cancer invasion and migration, but few studies have investigated in vivo how tumour pH correlates with cancer invasion. This study aims to determine in vivo whether tumour acidity is associated with cancer metastatic potential. Breast cancer cell lines with different metastatic potentials have been characterised for several markers of aggressiveness and invasiveness. Murine tumour models have been developed and assessed for lung metastases and tumour acidosis has been assessed in vivo by a magnetic resonance imaging-based chemical exchange saturation transfer (CEST) pH imaging approach. The higher metastatic potential of 4T1 and TS/A primary tumours, in comparison to the less aggressive TUBO and BALB-neuT ones, was confirmed by the highest expression of cancer cell stem markers (CD44 The findings of this study indicate that the extracellular acidification is associated with the metastatic potential.
Sections du résumé
BACKGROUND
Tumour acidosis is considered to play a central role in promoting cancer invasion and migration, but few studies have investigated in vivo how tumour pH correlates with cancer invasion. This study aims to determine in vivo whether tumour acidity is associated with cancer metastatic potential.
METHODS
Breast cancer cell lines with different metastatic potentials have been characterised for several markers of aggressiveness and invasiveness. Murine tumour models have been developed and assessed for lung metastases and tumour acidosis has been assessed in vivo by a magnetic resonance imaging-based chemical exchange saturation transfer (CEST) pH imaging approach.
RESULTS
The higher metastatic potential of 4T1 and TS/A primary tumours, in comparison to the less aggressive TUBO and BALB-neuT ones, was confirmed by the highest expression of cancer cell stem markers (CD44
CONCLUSIONS
The findings of this study indicate that the extracellular acidification is associated with the metastatic potential.
Identifiants
pubmed: 33257841
doi: 10.1038/s41416-020-01173-0
pii: 10.1038/s41416-020-01173-0
pmc: PMC7782702
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
207-216Subventions
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 667510
Organisme : Compagnia di San Paolo (Fondazione Compagnia di San Paolo)
ID : CSTO165925
Organisme : Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)
ID : IG 21468
Organisme : Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)
ID : ID 20153
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Références
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J. & Thun, M. J. Cancer statistics, 2009. Cancer J. Clin. 59, 225–249 (2009).
doi: 10.3322/caac.20006
Talmadge, J. E. & Fidler, I. J. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 70, 5649–5669 (2010).
pubmed: 20610625
pmcid: 4037932
doi: 10.1158/0008-5472.CAN-10-1040
Weigelt, B., Peterse, J. L. & van ‘t Veer, L. J. Breast cancer metastasis: markers and models. Nat. Rev. Cancer 5, 591–602 (2005).
pubmed: 16056258
doi: 10.1038/nrc1670
pmcid: 16056258
Dong, F., Budhu, A. S. & Wang, X. W. Translating the metastasis paradigm from scientific theory to clinical oncology. Clin. Cancer Res. 15, 2588–2593 (2009).
pubmed: 19351761
pmcid: 2683353
doi: 10.1158/1078-0432.CCR-08-2356
Page, D. L. Prognosis and breast cancer. Recognition of lethal and favorable prognostic types. Am. J. Surg. Pathol. 15, 334–349 (1991).
pubmed: 2006713
doi: 10.1097/00000478-199104000-00002
pmcid: 2006713
Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).
pubmed: 21376230
pmcid: 21376230
doi: 10.1016/j.cell.2011.02.013
Kakkad, S., Krishnamachary, B., Jacob, D., Pacheco-Torres, J., Goggins, E., Bharti, S. K. et al. Molecular and functional imaging insights into the role of hypoxia in cancer aggression. Cancer Metastasis Rev. https://doi.org/10.1007/s10555-019-09788-3 (2019).
doi: 10.1007/s10555-019-09788-3
pubmed: 30840168
pmcid: 6625878
Gillies, R. J., Robey, I. & Gatenby, R. A. Causes and consequences of increased glucose metabolism of cancers. J. Nucl. Med. 49(Suppl. 2), 24S–42S (2008).
pubmed: 18523064
doi: 10.2967/jnumed.107.047258
pmcid: 18523064
Damaghi, M., Wojtkowiak, J. W. & Gillies, R. J. pH sensing and regulation in cancer. Front. Physiol. 4, 370 (2013).
pubmed: 24381558
pmcid: 3865727
doi: 10.3389/fphys.2013.00370
Viklund, J., Avnet, S. & De Milito, A. Pathobiology and therapeutic implications of tumor acidosis. Curr. Med. Chem. 24, 2827–2845 (2017).
pubmed: 28031009
doi: 10.2174/0929867323666161228142849
Korenchan, D. E. & Flavell, R. R. Spatiotemporal pH heterogeneity as a promoter of cancer progression and therapeutic resistance. Cancers 11, 1026 (2019).
pmcid: 6678451
doi: 10.3390/cancers11071026
pubmed: 6678451
Bhujwalla, Z. M., Artemov, D., Natarajan, K., Ackerstaff, E. & Solaiyappan, M. Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts. Neoplasia 3, 143–153 (2001).
pubmed: 11420750
pmcid: 1505415
doi: 10.1038/sj.neo.7900129
Bharti, S. K., Kakkad, S., Danhier, P., Wildes, F., Penet, M. F., Krishnamachary, B. et al. Hypoxia patterns in primary and metastatic prostate cancer environments. Neoplasia 21, 239–246 (2019).
pubmed: 30639975
pmcid: 6327878
doi: 10.1016/j.neo.2018.12.004
Xu, H. N., Nioka, S., Glickson, J. D., Chance, B. & Li, L. Z. Quantitative mitochondrial redox imaging of breast cancer metastatic potential. J. Biomed. Opt. 15, 036010 (2010).
pubmed: 20615012
pmcid: 3188620
doi: 10.1117/1.3431714
Winnard, P. T. Jr., Pathak, A. P., Dhara, S., Cho, S. Y., Raman, V. & Pomper, M. G. Molecular imaging of metastatic potential. J. Nucl. Med. 49(Suppl. 2), 96S–112S (2008).
pubmed: 18523068
pmcid: 5516907
doi: 10.2967/jnumed.107.045948
Matsuo, M., Matsumoto, S., Mitchell, J. B., Krishna, M. C. & Camphausen, K. Magnetic resonance imaging of the tumor microenvironment in radiotherapy: perfusion, hypoxia, and metabolism. Semin. Radiat. Oncol. 24, 210–217 (2014).
pubmed: 24931096
pmcid: 4060050
doi: 10.1016/j.semradonc.2014.02.002
Chan, K. W., Jiang, L., Cheng, M., Wijnen, J. P., Liu, G., Huang, P. et al. CEST-MRI detects metabolite levels altered by breast cancer cell aggressiveness and chemotherapy response. NMR Biomed. 29, 806–816 (2016).
pubmed: 27100284
pmcid: 4873340
doi: 10.1002/nbm.3526
van der Kemp, W. J. M., van der Velden, T. A., Schmitz, A. M., Gilhuijs, K. G., Luijten, P. R., Klomp, D. W. J. et al. Shortening of apparent transverse relaxation time of inorganic phosphate as a breast cancer biomarker. NMR Biomed. https://doi.org/10.1002/nbm.4011 , e4011 (2018).
Bok, R., Lee, J., Sriram, R., Keshari, K., Sukumar, S., Daneshmandi, S. et al. The role of lactate metabolism in prostate cancer progression and metastases revealed by dual-agent hyperpolarized (13)C MRSI. Cancers 11, 257 (2019).
pmcid: 6406929
doi: 10.3390/cancers11020257
pubmed: 6406929
Hashim, A. I., Zhang, X., Wojtkowiak, J. W., Martinez, G. V. & Gillies, R. J. Imaging pH and metastasis. NMR Biomed. 24, 582–591 (2011).
pubmed: 21387439
pmcid: 3740268
doi: 10.1002/nbm.1644
Anemone, A., Consolino, L., Arena, F., Capozza, M. & Longo, D. L. Imaging tumor acidosis: a survey of the available techniques for mapping in vivo tumor pH. Cancer Metastasis Rev. 38, 25–49 (2019).
pubmed: 30762162
pmcid: 6647493
doi: 10.1007/s10555-019-09782-9
Longo, D. L., Dastru, W., Digilio, G., Keupp, J., Langereis, S., Lanzardo, S. et al. Iopamidol as a responsive MRI-chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T. Magn. Reson. Med. 65, 202–211 (2011).
pubmed: 20949634
doi: 10.1002/mrm.22608
Longo, D. L., Sun, P. Z., Consolino, L., Michelotti, F. C., Uggeri, F. & Aime, S. A general MRI-CEST ratiometric approach for pH imaging: demonstration of in vivo pH mapping with iobitridol. J. Am. Chem. Soc. 136, 14333–14336 (2014).
pubmed: 25238643
pmcid: 4210149
doi: 10.1021/ja5059313
Chen, L. Q., Howison, C. M., Jeffery, J. J., Robey, I. F., Kuo, P. H. & Pagel, M. D. Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI. Magn. Reson. Med. 72, 1408–1417 (2014).
pubmed: 24281951
doi: 10.1002/mrm.25053
Longo, D. L., Bartoli, A., Consolino, L., Bardini, P., Arena, F., Schwaiger, M. et al. In vivo imaging of tumor metabolism and acidosis by combining PET and MRI-CEST pH imaging. Cancer Res. 76, 6463–6470 (2016).
pubmed: 27651313
pmcid: 27651313
doi: 10.1158/0008-5472.CAN-16-0825
Anemone, A., Consolino, L., Conti, L., Reineri, F., Cavallo, F., Aime, S. et al. In vivo evaluation of tumour acidosis for assessing the early metabolic response and onset of resistance to dichloroacetate by using magnetic resonance pH imaging. Int. J. Oncol. 51, 498–506 (2017).
pubmed: 28714513
doi: 10.3892/ijo.2017.4029
Albatany, M., Li, A., Meakin, S. & Bartha, R. Dichloroacetate induced intracellular acidification in glioblastoma: in vivo detection using AACID-CEST MRI at 9.4 Tesla. J. Neurooncol. 136, 255–262 (2018).
pubmed: 29143921
doi: 10.1007/s11060-017-2664-9
Akhenblit, P. J. & Pagel, M. D. Recent advances in targeting tumor energy metabolism with tumor acidosis as a biomarker of drug efficacy. J. Cancer Sci. Ther. 8, 20–29 (2016).
pubmed: 26962408
pmcid: 4780427
doi: 10.4172/1948-5956.1000382
McVicar, N., Li, A. X., Meakin, S. O. & Bartha, R. Imaging chemical exchange saturation transfer (CEST) effects following tumor-selective acidification using lonidamine. NMR Biomed. 28, 566–575 (2015).
pubmed: 25808190
doi: 10.1002/nbm.3287
Anemone, A., Consolino, L. & Longo, D. L. MRI-CEST assessment of tumour perfusion using X-ray iodinated agents: comparison with a conventional Gd-based agent. Eur. Radiol. 27, 2170–2179 (2017).
pubmed: 27572810
doi: 10.1007/s00330-016-4552-7
pmcid: 27572810
Longo, D. L., Michelotti, F., Consolino, L., Bardini, P., Digilio, G., Xiao, G. et al. In vitro and in vivo assessment of nonionic iodinated radiographic molecules as chemical exchange saturation transfer magnetic resonance imaging tumor perfusion agents. Invest. Radiol. 51, 155–162 (2016).
pubmed: 26460826
doi: 10.1097/RLI.0000000000000217
pmcid: 26460826
Jones, K. M., Randtke, E. A., Yoshimaru, E. S., Howison, C. M., Chalasani, P., Klein, R. R. et al. Clinical translation of tumor acidosis measurements with AcidoCEST MRI. Mol. Imaging Biol. 19, 617–625 (2017).
pubmed: 27896628
pmcid: 6010170
doi: 10.1007/s11307-016-1029-7
Lanzardo, S., Conti, L., Rooke, R., Ruiu, R., Accart, N., Bolli, E. et al. Immunotargeting of antigen xCT attenuates stem-like cell behavior and metastatic progression in breast cancer. Cancer Res. 76, 62–72 (2016).
pubmed: 26567138
doi: 10.1158/0008-5472.CAN-15-1208
pmcid: 26567138
Pulaski, B. A. & Ostrand-Rosenberg, S. in Current Protocols Immunology (eds Coligan, J. E. et al.), Chapter 20, Unit 20.2 (2001).
Nanni, P., de Giovanni, C., Lollini, P. L., Nicoletti, G. & Prodi, G. TS/A: a new metastasizing cell line from a BALB/c spontaneous mammary adenocarcinoma. Clin. Exp. Metastasis 1, 373–380 (1983).
pubmed: 6546207
doi: 10.1007/BF00121199
pmcid: 6546207
Corbet, C., Draoui, N., Polet, F., Pinto, A., Drozak, X., Riant, O. et al. The SIRT1/HIF2alpha axis drives reductive glutamine metabolism under chronic acidosis and alters tumor response to therapy. Cancer Res. 74, 5507–5519 (2014).
pubmed: 25085245
doi: 10.1158/0008-5472.CAN-14-0705
pmcid: 25085245
Wyart, E., Reano, S., Hsu, M. Y., Longo, D. L., Li, M., Hirsch, E. et al. Metabolic alterations in a slow-paced model of pancreatic cancer-induced wasting. Oxid. Med. Cell. Longev. 2018, 6419805 (2018).
pubmed: 29682162
pmcid: 5846462
doi: 10.1155/2018/6419805
Hynes, J., O’Riordan, T. C., Zhdanov, A. V., Uray, G., Will, Y. & Papkovsky, D. B. In vitro analysis of cell metabolism using a long-decay pH-sensitive lanthanide probe and extracellular acidification assay. Anal. Biochem. 390, 21–28 (2009).
pubmed: 19379702
doi: 10.1016/j.ab.2009.04.016
pmcid: 19379702
Quaglino, E. & Cavallo, F. Immunological prevention of spontaneous tumors: a new prospect? Immunol. Lett. 80, 75–79 (2002).
Conti, L., Lanzardo, S., Arigoni, M., Antonazzo, R., Radaelli, E., Cantarella, D. et al. The noninflammatory role of high mobility group box 1/Toll-like receptor 2 axis in the self-renewal of mammary cancer stem cells. FASEB J. 27, 4731–4744 (2013).
pubmed: 23970797
doi: 10.1096/fj.13-230201
pmcid: 23970797
Charafe-Jauffret, E., Ginestier, C., Iovino, F., Wicinski, J., Cervera, N., Finetti, P. et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. 69, 1302–1313 (2009).
pubmed: 19190339
pmcid: 2819227
doi: 10.1158/0008-5472.CAN-08-2741
Senbanjo, L. T. & Chellaiah, M. A. CD44: a multifunctional cell surface adhesion receptor is a regulator of progression and metastasis of cancer cells. Front. Cell Dev. Biol. 5, 18 (2017).
pubmed: 28326306
pmcid: 5339222
doi: 10.3389/fcell.2017.00018
Hulikova, A., Aveyard, N., Harris, A. L., Vaughan-Jones, R. D. & Swietach, P. Intracellular carbonic anhydrase activity sensitizes cancer cell pH signaling to dynamic changes in CO2 partial pressure. J. Biol. Chem. 289, 25418–25430 (2014).
pubmed: 25059669
pmcid: 4162147
doi: 10.1074/jbc.M114.547844
Moellering, R. E., Black, K. C., Krishnamurty, C., Baggett, B. K., Stafford, P., Rain, M. et al. Acid treatment of melanoma cells selects for invasive phenotypes. Clin. Exp. Metastasis 25, 411–425 (2008).
pubmed: 18301995
doi: 10.1007/s10585-008-9145-7
pmcid: 18301995
Robey, I. F., Baggett, B. K., Kirkpatrick, N. D., Roe, D. J., Dosescu, J., Sloane, B. F. et al. Bicarbonate increases tumor pH and inhibits spontaneous metastases. Cancer Res. 69, 2260–2268 (2009).
pubmed: 19276390
pmcid: 2834485
doi: 10.1158/0008-5472.CAN-07-5575
Walenta, S., Wetterling, M., Lehrke, M., Schwickert, G., Sundfor, K., Rofstad, E. K. et al. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res. 60, 916–921 (2000).
pubmed: 10706105
pmcid: 10706105
Aboagye, E. O., Mori, N. & Bhujwalla, Z. M. Effect of malignant transformation on lactate levels of human mammary epithelial cells. Adv. Enzym. Regul. 41, 251–260 (2001).
doi: 10.1016/S0065-2571(00)00019-4
Pillai, S. R., Damaghi, M., Marunaka, Y., Spugnini, E. P., Fais, S. & Gillies, R. J. Causes, consequences, and therapy of tumors acidosis. Cancer Metastasis Rev. 38, 205–222 (2019).
pubmed: 30911978
pmcid: 6625890
doi: 10.1007/s10555-019-09792-7
Swietach, P. What is pH regulation, and why do cancer cells need it? Cancer Metastasis Rev. 38, 5–15 (2019).
pubmed: 30707328
pmcid: 6626545
doi: 10.1007/s10555-018-09778-x
Andersen, A. P., Flinck, M., Oernbo, E. K., Pedersen, N. B., Viuff, B. M. & Pedersen, S. F. Roles of acid-extruding ion transporters in regulation of breast cancer cell growth in a 3-dimensional microenvironment. Mol. Cancer 15, 45 (2016).
pubmed: 27266704
pmcid: 4896021
doi: 10.1186/s12943-016-0528-0
Fais, S. Evidence-based support for the use of proton pump inhibitors in cancer therapy. J. Transl. Med. 13, 368 (2015).
pubmed: 26597250
pmcid: 4657328
doi: 10.1186/s12967-015-0735-2
Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G. et al. Lactate metabolism in human lung tumors. Cell 171, 358–371 e359 (2017).
pubmed: 28985563
pmcid: 5684706
doi: 10.1016/j.cell.2017.09.019
Gatenby, R. A., Gawlinski, E. T., Gmitro, A. F., Kaylor, B. & Gillies, R. J. Acid-mediated tumor invasion: a multidisciplinary study. Cancer Res. 66, 5216–5223 (2006).
pubmed: 16707446
doi: 10.1158/0008-5472.CAN-05-4193
Ji, K., Mayernik, L., Moin, K. & Sloane, B. F. Acidosis and proteolysis in the tumor microenvironment. Cancer Metastasis Rev. 38, 103–112 (2019).
pubmed: 31069574
pmcid: 6886241
doi: 10.1007/s10555-019-09796-3
Chen, L. Q., Randtke, E. A., Jones, K. M., Moon, B. F., Howison, C. M. & Pagel, M. D. Evaluations of tumor acidosis within in vivo tumor models using parametric maps generated with AcidoCEST MRI. Mol. Imaging Biol. https://doi.org/10.1007/s11307-014-0816-2 (2015).
doi: 10.1007/s11307-014-0816-2
pubmed: 25962973
pmcid: 5218587
Wang, L., Fan, Z., Zhang, J., Changyi, Y., Huang, C., Gu, Y. et al. Evaluating tumor metastatic potential by imaging intratumoral acidosis via pH-activatable near-infrared fluorescent probe. Int. J. Cancer 136, E107–E116 (2015).
pubmed: 25155456
doi: 10.1002/ijc.29153
Rohani, N., Hao, L., Alexis, M. S., Joughin, B. A., Krismer, K., Moufarrej, M. N. et al. Acidification of tumor at stromal boundaries drives transcriptome alterations associated with aggressive phenotypes. Cancer Res. 79, 1952–1966 (2019).
pubmed: 30755444
pmcid: 6467770
doi: 10.1158/0008-5472.CAN-18-1604
Demoin, D. W., Wyatt, L. C., Edwards, K. J., Abdel-Atti, D., Sarparanta, M., Pourat, J. et al. PET imaging of extracellular pH in tumors with (64)Cu- and (18)F-labeled pHLIP peptides: a structure-activity optimization study. Bioconjugate Chem. 27, 2014–2023 (2016).
doi: 10.1021/acs.bioconjchem.6b00306
Nimmagadda, S., Pullambhatla, M., Stone, K., Green, G., Bhujwalla, Z. M. & Pomper, M. G. Molecular imaging of CXCR4 receptor expression in human cancer xenografts with [64Cu]AMD3100 positron emission tomography. Cancer Res. 70, 3935–3944 (2010).
pubmed: 20460522
pmcid: 2874192
doi: 10.1158/0008-5472.CAN-09-4396
Martinez, G. V., Zhang, X., Garcia-Martin, M. L., Morse, D. L., Woods, M., Sherry, A. D. et al. Imaging the extracellular pH of tumors by MRI after injection of a single cocktail of T1 and T2 contrast agents. NMR Biomed. 24, 1380–1391 (2011).
pubmed: 21604311
pmcid: 3693774
doi: 10.1002/nbm.1701
Lutz, N. W., Le Fur, Y., Chiche, J., Pouyssegur, J. & Cozzone, P. J. Quantitative in vivo characterization of intracellular and extracellular pH profiles in heterogeneous tumors: a novel method enabling multiparametric pH analysis. Cancer Res. 73, 4616–4628 (2013).
pubmed: 23752692
doi: 10.1158/0008-5472.CAN-13-0767
Chen, L. Q., Randtke, E. A., Jones, K. M., Moon, B. F., Howison, C. M. & Pagel, M. D. Evaluations of tumor acidosis within in vivo tumor models using parametric maps generated with Acido CEST MRI. Mol. Imaging Biol. 17, 488–496 (2015).
pubmed: 25622809
pmcid: 4880367
doi: 10.1007/s11307-014-0816-2
Consolino, L., Anemone, A., Capozza, M., Carella, A., Irrera, P., Corrado, A. et al. Non-invasive investigation of tumor metabolism and acidosis by MRI-CEST imaging. Front. Oncol. 10, 161 (2020).
pubmed: 32133295
pmcid: 7040491
doi: 10.3389/fonc.2020.00161
Voss, N. C. S., Dreyer, T., Henningsen, M. B., Vahl, P., Honore, B. & Boedtkjer, E. Targeting the acidic tumor microenvironment: unexpected pro-neoplastic effects of oral NaHCO3 therapy in murine breast tissue. Cancers 12, 891 (2020).
pmcid: 7226235
doi: 10.3390/cancers12040891
pubmed: 7226235
Kolosenko, I., Avnet, S., Baldini, N., Viklund, J. & De Milito, A. Therapeutic implications of tumor interstitial acidification. Semin. Cancer Biol. 43, 119–133 (2017).
pubmed: 28188829
doi: 10.1016/j.semcancer.2017.01.008