Wenjun Le, Bingdi Chen, Zheng Cui, Zhongmin Liu, Donglu Shi. Detection of cancer cells based on glycolytic-regulated surface electrical charges. Biophysics Reports, 2019, 5(1): 10-18. doi: 10.1007/s41048-018-0080-0
Citation: Wenjun Le, Bingdi Chen, Zheng Cui, Zhongmin Liu, Donglu Shi. Detection of cancer cells based on glycolytic-regulated surface electrical charges. Biophysics Reports, 2019, 5(1): 10-18. doi: 10.1007/s41048-018-0080-0

Detection of cancer cells based on glycolytic-regulated surface electrical charges

doi: 10.1007/s41048-018-0080-0
Funds:  This study was supported by National Natural Science Foundation of China (31671029, 81772285), Shanghai Natural Science Foundation (16ZR1400700), National Postdoctoral Program for Innovation Talents (BX201700173), and China Postdoctoral Science Foundation (2017M621534).
More Information
  • Corresponding author: Zhongmin Liu, Donglu Shi
  • Received Date: 29 May 2018
  • Rev Recd Date: 27 August 2018
  • Publish Date: 28 February 2019
  • Over the past decades, cell surface charge, although experimentally observed, has not been well understood particularly from the viewpoint of biophysics. Our recent studies have shown that all cancer cells exhibit negative surface charges that are directly proportional to the secreted lactic acid, a unique cancer metabolic characteristic: high rate of glycolysis. We have therefore designed and developed a set of electrically-charged, fluorescent, and super-paramagnetic nanoprobes, capable of sensitive detection of cancer cells based on the surface charges. These probes are utilized to bind onto cells via electrostatic reaction for capture and magnetic separation. In this fashion, we are able to characterize cell surface charges that are regulated by different metabolic patterns, therefore effectively distinguishing the cancer cells from the normal cells. All 22 cancer cells of different organs are found to be negativelycharged therefore bound strongly by the positively-charged nanoprobes, whereas the normal cells show insignificant binding to the nanoprobes of either charge signs (positive or negative). This finding suggests that all tested cancer cells are negatively-charged and normal cells are either charge-neutral or slightly positive. For diagnosis, cancer cells can be detected, electrostatically bound, and magnetically separated in blood by charged and super-paramagnetic nanoprobes. In therapeutics, circulating cancer cells (CTCs) can be filtered and removed in a continuous fashion to reduce the risk of cancer metastasis. If successful, this new nanotechnology will revolutionize early cancer diagnosis and potentially enable new therapeutics in clinical settings.
  • loading
  • Ambrose EJ, James AM, Lowick JHB (1956) Differences between the electrical charge carried by normal and homologous tumour cells. Nature 177(4508):576
    Ashworth TR (1869) A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J 14:146
    Blanks MJ, Stehle JR, Du W, Adams JM, Willingham MC, Allen GO, Hu JJ, Lovato J, Molnar I, Cui Z (2011) Novel innate cancer killing activity in humans. Cancer Cell Int 11(1):26
    Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, Matos C, Bruss C, Klobuch S, Peter K, Kastenberger M, Bogdan C, Schleicher U, Mackensen A, Ullrich E, Fichtner-Feigl S, Kesselring R, Mack M, Ritter U, Schmid M, Blank C, Dettmer K, Oefner PJ, Hoffmann P, Walenta S, Geissler EK, Pouyssegur J, Villunger A, Steven A, Seliger B, Schreml S, Haferkamp S, Kohl E, Karrer S, Berneburg M, Herr W, Mueller-Klieser W, Renner K, Kreutz M (2016) LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab 24(5):657-671
    Chaffer CL, Weinberg RA (2011) A perspective on cancer cell metastasis. Science 331(6024):1559-1564
    Chen B, Le W, Wang Y, Li Z, Wang D, Ren L, Lin L, Cui S, Hun JJ, Hu Y, Yang P, Ewing RC, Shi DL, Cui Z (2016) Targeting negative surface charges of cancer cells by multifunctional nanoprobes. Theranostics 6(11):1887
    Chikaishi Y, Yoneda K, Ohnaga T, Tanaka F (2017) EpCAMindependent capture of circulating tumor cells with a'universal CTC-chip'. Oncol Rep 37(1):77-82 Colegio OR, Chu NQ, Szabo AL, Chu T, Rhebergen AM, Jairam V, Cyrus N, Brokowski CE, Eisenbarth SC, Phillips GM, Cline GW, Phillips AJ, Medzhitov R (2014) Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513(7519):559
    Copeland L, Turner JF (1980) The regulation of glycolysis and the pentose phosphate pathway. In:Davies DD (ed) Metabolism and respiration. Academic Press, New York, pp 279-316 Cui Z (2011) Granular cell anticancer therapy. Tsinghua University Press, Beijing
    Cui Z, Willingham MC, Hicks AM, Alexander-Miller MA, Howard TD, Hawkins GA, Miller MS, Weir HM, Du W, DeLong CJ (2003) Spontaneous regression of advanced cancer:identification of a unique genetically determined, age-dependent trait in mice. Proc Natl Acad Sci USA 100(11):6682-6687
    De Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Doyle GV, Terstappen LW, Pienta KJ, Raghavan D (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14(19):6302-6309
    den Toonder J (2011) Circulating tumor cells:the grand challenge. Lab Chip 11(3):375-377
    Dubyak GR (2004) Ion homeostasis, channels, and transporters:an update on cellular mechanisms. Adv Physiol Educ 28(4):143-154
    Fu D, Mitra K, Sengupta P, Jarnik M, Lippincott-Schwartz J, Arias IM (2013) Coordinated elevation of mitochondrial oxidative phosphorylation and autophagy help drive hepatocyte polarization. Proc Natl Acad Sci USA 110(18):7288-7293
    Gadsby DC (2009) Ion channels versus ion pumps:the principal difference, in principle. Nat Rev Mol Cell Biol 10(5):344
    Gadsby DC, Takeuchi A, Artigas P, Reyes N (2009) Peering into an ATPase ion pump with single-channel recordings. Philos Trans R Soc B 364(1514):229-238
    Ghossein RA, Rosai J (1996) Polymerase chain reaction in the detection of micrometastases and circulating tumor cells. Cancer 78(1):10-16
    Ghossein RA, Scher HI, Gerald WL, Kelly WK, Curley T, Amsterdam A, Zhang ZF, Rosai J (1995) Detection of circulating tumor cells in patients with localized and metastatic prostatic carcinoma:clinical implications. J Clin Oncol 13(5):1195-1200
    Gogichadze G, Gogichadze T, Misabishvili E, Kamkamidze G (2014) Possible effect of variable membrane potential of a cancer cell on different carcinogenic processes. Georgian Med News 234:116-120
    Gorges TM, Tinhofer I, Drosch M, Roöse L, Zollner M, Krahn T, von Ahsen O (2012) Circulating tumour cells escape from EpCAMbased detection due to epithelial-to-mesenchymal transition. BMC Cancer 12(1):178
    Haber DA, Gray NS, Baselga J (2011) The evolving war on cancer. Cell 145(1):19-24
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer:the next generation. Cell 144(5):646-674
    Hatt M, Majdoub M, Vallières M, Tixier F, Le Rest CC, Groheux D, Hindié E, Martineau A, Pradier O, Hustinx R, Perdrisot R, Guillevin R, Naqa IE, Visvikis D (2015) 18F-FDG PET uptake characterization through texture analysis:investigating the complementary nature of heterogeneity and functional tumor volume in a multi-cancer site patient cohort. J Nucl Med 56(1):38-44
    Hicks AM, Riedlinger G, Willingham MC, Alexander-Miller MA, Von Kap-Herr C, Pettenati MJ, Sanders AM, Weir HM, Du W, Kim J, Simpson AJ, Old LJ, Cui Z (2006) Transferable anticancer innate immunity in spontaneous regression/complete resistance mice. Proc Natl Acad Sci USA 103(20):7753-7758
    Hosokawa M, Hayata T, Fukuda Y, Arakaki A, Yoshino T, Tanaka T, Matsunaga T (2010) Size-selective microcavity array for rapid and efficient detection of circulating tumor cells. Anal Chem 82(15):6629-6635
    Hsu PP, Sabatini DM (2008) Cancer cell metabolism:Warburg and beyond. Cell 134(5):703-707
    Hutchings M, Loft A, Hansen M, Pedersen LM, Buhl T, Jurlander J, Buus S, Keiding S, D'Amore F, Boesen A, Berthelsen AK, Lena Specht (2006) FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood 107(1):52-59
    Kim TH, Lim M, Park J, Oh JM, Kim H, Jeong H, Lee SJ, Park HC, Jung S, Kim BC, Lee K, Kim MH, Park DY, Kim GH, Cho YK (2016) FAST:size-selective, clog-free isolation of rare cancer cells from whole blood at a liquid-liquid interface. Anal Chem 89(2):1155-1162
    Kuismanen E, Saraste J (1989) Low temperature-induced transport blocks as tools to manipulate membrane traffic. Methods Cell Biol 3:257-274
    Lehrer RI, Lichtenstein AK, Ganz T (1993) Defensins:antimicrobial and cytotoxic peptides of mammalian cells. Annu Rev Immunol 11(1):105-128
    Li P, Mao Z, Peng Z, Zhou L, Chen Y, Huang PH, Truica CI, Drabick JJ, El-Deiry WS, Dao M, Suresh S, Huang TJ (2015) Acoustic separation of circulating tumor cells. Proc Natl Acad Sci USA 112(16):4970-4975
    Lu J, Tan M, Cai Q (2015) The Warburg effect in tumor progression:mitochondrial oxidative metabolism as an antimetastasis mechanism. Cancer Lett 356(2):156-164 McLaughlin PJ (1954) A history of the theories of aether and electricity. Philos Stud 4:118-119
    Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A (2016) Cancer treatment and survivorship statistics. CA:A Cancer J Clin 66(4):271-289
    Moon HS, Kwon K, Kim SI, Han H, Sohn J, Lee S, Jung HI (2011) Continuous separation of breast cancer cells from blood samples using multi-orifice flow fractionation (MOFF) and dielectrophoresis (DEP). Lab Chip 11(6):1118-1125
    Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Simth MR, Kwak EL, Diagumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkin RG, Haber DA, Toner M (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235
    Osaka T, Nakanishi T, Shanmugam S, Takahama S, Zhang H (2009) Effect of surface charge of magnetite nanoparticles on their internalization into breast cancer and umbilical vein endothelial cells. Colloids Surf, B 71(2):325-330
    Pestonjamasp VK, Mehta NG (1995) Erythrocytes from Yoshida ascites sarcoma-bearing rats have reduced surface charge:the effect of tumor products. Cancer Biochem Biophys 15(1):19-23
    Plaks V, Koopman CD, Werb Z (2013) Circulating tumor cells. Science 341(6151):1186-1188
    Pore M, Meijer C, de Bock GH, Boersma-van Ek W, Terstappen LW, Groen HJ, Timens W, Kruyt FAE, Hiltermann TJN (2016) Cancer stem cells, epithelial to mesenchymal markers, and circulating tumor cells in small cell lung cancer. Clin Lung Cancer 17(6):535-542
    Purdom L, Ambrose EJ, Klein G (1958) A correlation between electrical surface charge and some biological characteristics during the stepwise progression of a mouse sarcoma. Nature 181(4623):1586
    Racila E, Euhus D, Weiss AJ, Rao C, McConnell J, Terstappen LW, Uhr JW (1998) Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci USA 95(8):4589-4594
    Radovic-Moreno AF, Lu TK, Puscasu VA, Yoon CJ, Langer R, Farokhzad OC (2012) Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics. ACS Nano 6(5):4279-4287
    Riedlinger G, Adams J, Stehle JR, Blanks MJ, Sanders AM, Hicks AM, Willingham MC, Cui Z (2010) The spectrum of resistance in SR/CR mice:the critical role of chemoattraction in the cancer/leukocyte interaction. BMC Cancer 10(1):179
    Schell JC, Olson KA, Jiang L, Hawkins AJ, Van Vranken JG, Xie J, Egnatchik RA, DeBeradinis RJ, Rutter J (2014) A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell 56(3):400-413
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA:A Cancer J Clin 67:7-30
    Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2008. Ca:A Cancer J Clin 68:5-29
    Sonders MS, Amara SG (1996) Channels in transporters. Curr Opin Neurobiol 6(3):294-302
    Stewart B, Wild CP (2014) World cancer report 2014 Tellez-Gabriel M, Brown HK, Young R, Heymann MF, Heymann D (2016) The challenges of detecting circulating tumor cells in sarcoma. Front Oncol 6:202
    Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect:the metabolic requirements of cell proliferation. Science 324(5930):1029-1033
    Vassar PS (1963) Electrophoretic mobility of human tumour cells. Nature 197(4873):1215-1216
    Vyas S, Zaganjor E, Haigis MC (2016) Mitochondria and cancer. Cell 166(3):555-566
    Warburg O (1924) Über den stoffwechsel der carcinomzelle. Naturwissenschaften 12(50):1131-1137
    Warburg O (1956) On the origin of cancer cells. Science 123(3191):309-314
    Yoon HJ, Kim TH, Zhang Z, Azizi E, Pham TM, Paoletti C, Lin J, Ramnath N, Wicha MS, Hayes DF, Simeone DM, Nagrath S (2013) Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nat Nanotechnol 8(10):735
    Yoshii T, Geng Y, Peyton S, Mercurio AM, Rotello VM (2016) Biochemical and biomechanical drivers of cancer cell metastasis, drug response and nanomedicine. Drug Discov Today 21(9):1489-1494
    You JS, Jones PA (2012) Cancer genetics and epigenetics:two sides of the same coin? Cancer Cell 22(1):9-20
    Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Concannon KF (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339:580-584
    Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, Desai R, Zhu H, Comaills V, Zheng Z, Wittner BS, Petar Stojanov, Brachtel E, Sgroi D, Kapur R, Shioda T, Ting DT, Ramaswamy S, Getz G, Iafrate AJ, Benes C, Toner M, Maheswaran S, Harber D (2014) Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345(6193):216-220
    Zink D, Fischer AH, Nickerson JA (2004) Nuclear structure in cancer cells. Nat Rev Cancer 4(9):677
    Williams SCP (2013) Circulating tumor cells. Proc Natl Acad Sci USA 110(13):4861-4861
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (1770) PDF downloads(238) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint