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Detection and Isolation of Cancer Stem Cells

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Cancer Stem Cells: Basic Concept and Therapeutic Implications

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Abstract

The discovery and isolation of the hematopoietic stem cell (HSC) from bone marrow grafts introduced the concept of a cell type capable of restoring hematopoiesis in irradiated mice. The interest in a possible “leukemia stem cell” (LSC) gave rise to multiple studies using similar techniques to detect mature leukemic cells, which shared a biomarker profile with the HSC. Interests expanded to include solid cancers and resulted in adaptations of stem cell detection methods specifically for cancer stem cells (CSCs), which are rapidly improving. Here we discuss the development of these methods, their advantages and limitations, and highlight some detection targets which are featured consistently in the literature.

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Abbreviations

5-FU:

5-Fluororacil

ABCG2:

ATP-binding cassette G2

ALDH:

Aldehyde dehydrogenase

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

ASCL:

Achaete-scute complex

BAAA:

BODIPY-aminoacetaldehyde

BNX:

bg/nu/xid mice

CD:

Cluster of differentiation

CFU-S:

Colony-forming unit (spleen)

CSC:

Cancer stem cell

CTC:

Circulating tumor cell

CXCL12:

C-X-C chemokine ligand 12

CXCR4:

C-X-C chemokine receptor 4

DEAB:

Diethylaminobenzaldehyde

DNA:

Deoxyribonucleic acid

EGF:

Epithelial growth factor

EMT:

Epithelial-to-mesenchymal transition

EpCAM:

Epithelial cellular adhesion molecule

ESC:

Embryonic stem cell

FACS:

Fluorescence-activated cell sorting

FGF:

Fibroblast growth factor

FWGL:

Fluoresceinated wheat germ lectin

GM-CFU:

Granulocyte-macrophage colony-forming units

H33342:

Hoechst 33342 DNA dye

HIF:

Hypoxia-inducible factor

HSC:

Hematopoietic stem cell

LDA:

Limited dilution assay

LSC:

Leukemia stem cell

MAb:

Monoclonal antibody

MACS:

Magnetic-activated cell sorting

miRNA:

MicroRNA

Neu5Ac:

N-acetylneuraminic acid

NOD/SCID:

Nondiabetic/severe combined immunodeficiency

NSCLC:

Non-small cell lung cancer

RNA:

Ribonucleic acid

Sca-1:

Stem cell antigen-1

SCC:

Squamous cell carcinoma

SCLC:

Small cell lung cancer

SL-IC:

SCID-leukemia-initiating cell

SP:

Side population

TAM:

Tumor-associated macrophage

TPC:

Tumor-propagating cell

References

  • Addla SK, Brown MD, Hart CA, Ramani VAC, Clarke NW (2008) Characterization of the Hoechst 33342 side population from normal and malignant human renal epithelial cells. Am J Physiol Renal Physiol 295:F680–F687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100:3983–3988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alison MR, Lim SM, Nicholson LJ (2011) Cancer stem cells: problems for therapy? J Pathol 223:148–162

    Article  Google Scholar 

  • Alvero AB, Chen R, Fu HH, Montagna M, Schwartz PE, Rutherford T, Silasi DA, Steffensen KD, Waldstrom M, Visintin I, Mor G (2009) Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance. Cell Cycle 8:158–166

    Article  CAS  PubMed  Google Scholar 

  • Azevedo R, Gaiteiro C, Peixoto A, Relvas-Santos M, Lima L, Santos LL, Ferreira JA (2018) CD44 glycoprotein in cancer: a molecular conundrum hampering clinical applications. Clin Proteomics 15:22

    Article  PubMed  PubMed Central  Google Scholar 

  • Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, Huang Z, Bentley RC, Mori S, Fujii S, Marks JR, Berchuck A, Murphy SK (2009) Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene 28:209–218

    Article  CAS  PubMed  Google Scholar 

  • Baines P, Visser JW (1983) Analysis and separation of murine bone marrow stem cells by H33342 fluorescence-activated cell sorting. Exp Hematol 11:701–708

    CAS  PubMed  Google Scholar 

  • Bapat SA, Mali AM, Koppikar CB, Kurrey NK (2005) Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 65:3025–3029

    Article  CAS  PubMed  Google Scholar 

  • Batlle E, Clevers H (2017) Cancer stem cells revisited. Nat Med 23:1124–1134

    Article  CAS  PubMed  Google Scholar 

  • Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T, Yagita H, Sleeman JP (2005) CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res 65:10783–10793

    Article  CAS  PubMed  Google Scholar 

  • Becker AJ, Mc CE, Till JE (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452–454

    Article  CAS  PubMed  Google Scholar 

  • Benveniste P, Cantin C, Hyam D, Iscove NN (2003) Hematopoietic stem cells engraft in mice with absolute efficiency. Nat Immunol 4:708–713

    Article  CAS  PubMed  Google Scholar 

  • Bhaskara VK, Mohanam I, Rao JS, Mohanam S (2012) Intermittent hypoxia regulates stem-like characteristics and differentiation of neuroblastoma cells. PLoS One 7:e30905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bianco C, Patrick R, Nussenzweig V (1970) A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization. J Exp Med 132:702–720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonner WA, Hulett HR, Sweet RG, Herzenberg LA (1972) Fluorescence activated cell sorting. Rev Sci Instrum 43:404–409

    Article  CAS  PubMed  Google Scholar 

  • Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737

    Article  CAS  PubMed  Google Scholar 

  • Bortolomai I, Canevari S, Facetti I, De Cecco L, Castellano G, Zacchetti A, Alison MR, Miotti S (2010) Tumor initiating cells: development and critical characterization of a model derived from the A431 carcinoma cell line forming spheres in suspension. Cell Cycle 9:1194–1206

    Article  CAS  PubMed  Google Scholar 

  • Bruno S, Bussolati B, Grange C, Collino F, Graziano ME, Ferrando U, Camussi G (2006) CD133+ renal progenitor cells contribute to tumor angiogenesis. Am J Pathol 169:2223–2235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buckner CDE, Rudolph RB, Clift RH, Storb RA, Thomas R, Donnall E (1970) Allogeneic marrow engraftment following whole body irradiation in a patient with leukemia. Blood 35:741–750

    Article  CAS  PubMed  Google Scholar 

  • Carpentino JE, Hynes MJ, Appelman HD, Zheng T, Steindler DA, Scott EW, Huang EH (2009) Aldehyde dehydrogenase–expressing colon stem cells contribute to tumorigenesis in the transition from colitis to cancer. Cancer Res 69:8208–8215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Charafe-Jauffret E, Ginestier C, Iovino F, Tarpin C, Diebel M, Esterni B, Houvenaeghel G, Extra J-M, Bertucci F, Jacquemier J, Xerri L, Dontu G, Stassi G, Xiao Y, Barsky SH, Birnbaum D, Viens P, Wicha MS (2010) Aldehyde dehydrogenase 1–positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res 16:45–55

    Article  CAS  PubMed  Google Scholar 

  • Chen T, Yang K, Yu J, Meng W, Yuan D, Bi F, Liu F, Liu J, Dai B, Chen X, Wang F, Zeng F, Xu H, Hu J, Mo X (2012) Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients. Cell Res 22:248–258

    Article  CAS  PubMed  Google Scholar 

  • Chen Y-C, Chen Y-W, Hsu H-S, Tseng L-M, Huang P-I, Lu K-H, Chen D-T, Tai L-K, Yung M-C, Chang S-C, Ku H-H, Chiou S-H, Lo W-L (2009) Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. Biochem Biophys Res Commun 385:307–313

    Article  CAS  PubMed  Google Scholar 

  • Chen Y-C, Hsu H-S, Chen Y-W, Tsai T-H, How C-K, Wang C-Y, Hung S-C, Chang Y-L, Tsai M-L, Lee Y-Y, Ku H-H, Chiou S-H (2008) Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS One 3:e2637

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheng JX, Liu BL, Zhang X (2009) How powerful is CD133 as a cancer stem cell marker in brain tumors? Cancer Treat Rev 35:403–408

    Article  CAS  PubMed  Google Scholar 

  • Cheung AMS, Wan TSK, Leung JCK, Chan LYY, Huang H, Kwong YL, Liang R, Leung AYH (2007) Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential. Leukemia 21:1423–1430

    Article  CAS  PubMed  Google Scholar 

  • Chiba T, Miyagi S, Saraya A, Aoki R, Seki A, Morita Y, Yonemitsu Y, Yokosuka O, Taniguchi H, Nakauchi H, Iwama A (2008) The Polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. Cancer Res 68:7742–7749

    Article  CAS  PubMed  Google Scholar 

  • Chiodi I, Belgiovine C, Donà F, Scovassi AI, Mondello C (2011) Drug treatment of cancer cell lines: a way to select for cancer stem cells? Cancers (Basel) 3:1111–1128

    Article  CAS  PubMed  Google Scholar 

  • Chu P, Clanton DJ, Snipas TS, Lee J, Mitchell E, Nguyen M-L, Hare E, Peach RJ (2009) Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer 124:1312–1321

    Article  CAS  PubMed  Google Scholar 

  • Civin CI, Strauss LC, Brovall C, Fackler MJ, Schwartz JF, Shaper JH (1984) Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol 133:157–165

    Article  CAS  PubMed  Google Scholar 

  • Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951

    Article  CAS  PubMed  Google Scholar 

  • Cox CV, Diamanti P, Evely RS, Kearns PR, Blair A (2009) Expression of CD133 on leukemia-initiating cells in childhood ALL. Blood 113:3287–3296

    Article  CAS  PubMed  Google Scholar 

  • Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 104:10158–10163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Darash-Yahana M, Pikarsky E, Abramovitch R, Zeira E, Pal B, Karplus R, Beider K, Avniel S, Kasem S, Galun E, Peled A (2004) Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis. FASEB J 18:1240–1242

    Article  CAS  PubMed  Google Scholar 

  • Das B, Tsuchida R, Malkin D, Koren G, Baruchel S, Yeger H (2008) Hypoxia enhances tumor stemness by increasing the invasive and tumorigenic side population fraction. Stem Cells 26:1818–1830

    Article  PubMed  Google Scholar 

  • Deng Z, Wu Y, Ma W, Zhang S, Zhang YQ (2015) Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunol 16:1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dick JE (2008) Stem cell concepts renew cancer research. Blood 112:4793–4807

    Article  CAS  PubMed  Google Scholar 

  • Dontu G, Al-Hajj M, Abdallah WM, Clarke MF, Wicha MS (2003) Stem cells in normal breast development and breast cancer. Cell Prolif 36(Suppl 1):59–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du L, Wang H, He L, Zhang J, Ni B, Wang X, Jin H, Cahuzac N, Mehrpour M, Lu Y, Chen Q (2008) CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res 14:6751–6760

    Article  CAS  PubMed  Google Scholar 

  • Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C, De Maria R (2008) Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 15:504–514

    Article  CAS  PubMed  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    Article  CAS  PubMed  Google Scholar 

  • Fillmore CM, Kuperwasser C (2008) Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 10:R25

    Article  PubMed  PubMed Central  Google Scholar 

  • Friel AM, Sergent PA, Patnaude C, Szotek PP, Oliva E, Scadden DT, Seiden MV, Foster R, Rueda BR (2008) Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells. Cell Cycle 7:242–249

    Article  CAS  PubMed  Google Scholar 

  • Fujikuni N, Yamamoto H, Tanabe K, Naito Y, Sakamoto N, Tanaka Y, Yanagihara K, Oue N, Yasui W, Ohdan H (2014) Hypoxia-mediated CD24 expression is correlated with gastric cancer aggressiveness by promoting cell migration and invasion. Cancer Sci 105:1411–1420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fuss IJ (2020) Purification of T cell populations. Curr Protoc Immunol 128:e94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021

    Article  CAS  PubMed  Google Scholar 

  • Gao MQ, Choi YP, Kang S, Youn JH, Cho NH (2010) CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells. Oncogene 29:2672–2680

    Article  CAS  PubMed  Google Scholar 

  • Gassenmaier M, Chen D, Buchner A, Henkel L, Schiemann M, Mack B, Schendel DJ, Zimmermann W, Pohla H (2013) CXC chemokine receptor 4 is essential for maintenance of renal cell carcinoma-initiating cells and predicts metastasis. Stem Cells 31:1467–1476

    Article  CAS  PubMed  Google Scholar 

  • Gatti R, Meuwissen H, Allen H, Hong R, Good R (1968) Immunological reconstitution of sex-linked Lymphopenic immunological deficiency. Lancet 292:1366–1369

    Article  Google Scholar 

  • Ghuwalewala S, Ghatak D, Das P, Dey S, Sarkar S, Alam N, Panda CK, Roychoudhury S (2016) CD44(high)CD24(low) molecular signature determines the cancer stem cell and EMT phenotype in oral squamous cell carcinoma. Stem Cell Res 16:405–417

    Article  CAS  PubMed  Google Scholar 

  • Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gold ER, Fudenberg HH (1967) Chromic chloride: a coupling reagent for passive hemagglutination reactions. J Immunol 99:859–866

    Article  CAS  PubMed  Google Scholar 

  • Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183:1797–1806

    Article  CAS  PubMed  Google Scholar 

  • Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2:48–58

    Article  CAS  PubMed  Google Scholar 

  • Greco A, Rizzo MI, De Virgilio A, Gallo A, Fusconi M, Pagliuca G, Martellucci S, Turchetta R, De Vincentiis M (2016) Cancer stem cells in laryngeal cancer: what we know. Eur Arch Otorhinolaryngol 273:3487–3495

    Article  CAS  PubMed  Google Scholar 

  • Guan Y, Gerhard B, Hogge DE (2003) Detection, isolation, and stimulation of quiescent primitive leukemic progenitor cells from patients with acute myeloid leukemia (AML). Blood 101:3142–3149

    Article  CAS  PubMed  Google Scholar 

  • Guenechea G, Gan OI, Dorrell C, Dick JE (2001) Distinct classes of human stem cells that differ in proliferative and self-renewal potential. Nat Immunol 2:75–82

    Article  CAS  PubMed  Google Scholar 

  • He J, Liu Y, Zhu T, Zhu J, Dimeco F, Vescovi AL, Heth JA, Muraszko KM, Fan X, Lubman DM (2012) CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays*. Mol Cell Proteomics:11

    Google Scholar 

  • Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci 100:15178–15183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313–323

    Article  CAS  PubMed  Google Scholar 

  • van den Hoogen C, Van Der Horst G, Cheung H, Buijs JT, Lippitt JM, Guzmán-Ramírez N, Hamdy FC, Eaton CL, Thalmann GN, Cecchini MG, Pelger RC, Van Der Pluijm G (2010) High aldehyde dehydrogenase activity identifies tumor-initiating and metastasis-initiating cells in human prostate cancer. Cancer Res 70:5163–5173

    Article  PubMed  Google Scholar 

  • Hope KJ, Jin L, Dick JE (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5:738–743

    Article  CAS  PubMed  Google Scholar 

  • Huang B, Huang YJ, Yao ZJ, Chen X, Guo SJ, Mao XP, Wang DH, Chen JX, Qiu SP (2013) Cancer stem cell-like side population cells in clear cell renal cell carcinoma cell line 769P. PLoS One 8:e68293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS, Boman BM (2009) Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res 69:3382–3389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang R, Rofstad EK (2017) Cancer stem cells (CSCs), cervical CSCs and targeted therapies. Oncotarget 8:35351–35367

    Article  PubMed  Google Scholar 

  • Huntly BJ, Gilliland DG (2005) Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 5:311–321

    Article  CAS  PubMed  Google Scholar 

  • Hurt EM, Kawasaki BT, Klarmann GJ, Thomas SB, Farrar WL (2008) CD44+CD24− prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br J Cancer 98:756–765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ignatova TN, Kukekov VG, Laywell ED, Suslov ON, Vrionis FD, Steindler DA (2002) Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 39:193–206

    Article  PubMed  Google Scholar 

  • Ishiwata T, Matsuda Y, Yoshimura H, Sasaki N, Ishiwata S, Ishikawa N, Takubo K, Arai T, Aida J (2018) Pancreatic cancer stem cells: features and detection methods. Pathol Oncol Res 24:797–805

    Article  CAS  PubMed  Google Scholar 

  • Jackson M, Hassiotou F, Nowak A (2015) Glioblastoma stem-like cells: at the root of tumor recurrence and a therapeutic target. Carcinogenesis 36:177–185

    Article  CAS  PubMed  Google Scholar 

  • Jariyal H, Gupta C, Bhat VS, Wagh JR, Srivastava A (2019) Advancements in cancer stem cell isolation and characterization. Stem Cell Rev Rep 15:755–773

    Article  PubMed  Google Scholar 

  • Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, Wang H, Liu Z, Su Y, Stass SA, Katz RL (2009a) Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res 7:330–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang T, Collins BJ, Jin N, Watkins DN, Brock MV, Matsui W, Nelkin BD, Ball DW (2009b) Achaete-scute complex homologue 1 regulates tumor-initiating capacity in human small cell lung cancer. Cancer Res 69:845–854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones RJ, Gocke CD, Kasamon YL, Miller CB, Perkins B, Barber JP, Vala MS, Gerber JM, Gellert LL, Siedner M, Lemas MV, Brennan S, Ambinder RF, Matsui W (2009) Circulating clonotypic B cells in classic Hodgkin lymphoma. Blood 113:5920–5926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamel-Reid S, Dick JE (1988) Engraftment of immune-deficient mice with human hematopoietic stem cells. Science 242:1706–1709

    Article  CAS  PubMed  Google Scholar 

  • Kato K, Takao T, Kuboyama A, Tanaka Y, Ohgami T, Yamaguchi S, Adachi S, Yoneda T, Ueoka Y, Kato K, Hayashi S, Asanoma K, Wake N (2010) Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage. Am J Pathol 176:381–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kerr BA, Miocinovic R, Smith AK, West XZ, Watts KE, Alzayed AW, Klink JC, Mir MC, Sturey T, Hansel DE, Heston WD, Stephenson AJ, Klein EA, Byzova TV (2015) CD117+ cells in the circulation are predictive of advanced prostate cancer. Oncotarget 6:1889–1897

    Article  PubMed  Google Scholar 

  • Kim RJ, Park JR, Roh KJ, Choi AR, Kim SR, Kim PH, Yu JH, Lee JW, Ahn SH, Gong G, Hwang JW, Kang KS, Kong G, Sheen YY, Nam JS (2013) High aldehyde dehydrogenase activity enhances stem cell features in breast cancer cells by activating hypoxia-inducible factor-2α. Cancer Lett 333:18–31

    Article  CAS  PubMed  Google Scholar 

  • Klarmann GJ, Hurt EM, Mathews LA, Zhang X, Duhagon MA, Mistree T, Thomas SB, Farrar WL (2009) Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature. Clin Exp Metastasis 26:433–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kraft A (2009) Manhattan transfer: lethal radiation, bone marrow transplantation, and the birth of stem cell biology, ca. 1942–1961. Hist Stud Nat Sci 39:171–218

    Article  PubMed  Google Scholar 

  • Krohn A, Song Y-H, Muehlberg F, Droll L, Beckmann C, Alt E (2009) CXCR4 receptor positive spheroid forming cells are responsible for tumor invasion in vitro. Cancer Lett 280:65–71

    Article  CAS  PubMed  Google Scholar 

  • Kryczek I, Liu S, Roh M, Vatan L, Szeliga W, Wei S, Banerjee M, Mao Y, Kotarski J, Wicha MS, Liu R, Zou W (2012) Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells. Int J Cancer 130:29–39

    Article  CAS  PubMed  Google Scholar 

  • Lapidot T, Pflumio F, Doedens M, Murdoch B, Williams DE, Dick JE (1992) Cytokine stimulation of multilineage hematopoiesis from immature human cells engrafted in SCID mice. Science 255:1137–1141

    Article  CAS  PubMed  Google Scholar 

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367:645–648

    Article  CAS  PubMed  Google Scholar 

  • Larochelle A, Vormoor J, Hanenberg H, Wang JCY, Bhatia M, Lapidot T, Moritz T, Murdoch B, Xiao XL, Kato I, Williams DA, Dick JE (1996) Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy. Nat Med 2:1329–1337

    Article  CAS  PubMed  Google Scholar 

  • Lau WM, Teng E, Chong HS, Lopez KA, Tay AY, Salto-Tellez M, Shabbir A, So JB, Chan SL (2014) CD44v8-10 is a cancer-specific marker for gastric cancer stem cells. Cancer Res 74:2630–2641

    Article  CAS  PubMed  Google Scholar 

  • Lee TK, Castilho A, Cheung VC, Tang KH, Ma S, Ng IO (2011) CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell 9:50–63

    Article  CAS  PubMed  Google Scholar 

  • Levina V, Marrangoni AM, Demarco R, Gorelik E, Lokshin AE (2008) Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties. PLoS One 3:e3077

    Article  PubMed  PubMed Central  Google Scholar 

  • Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037

    Article  CAS  PubMed  Google Scholar 

  • Li T, Su Y, Mei Y, Leng Q, Leng B, Liu Z, Stass SA, Jiang F (2010) ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome. Lab Investig 90:234–244

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, Mclendon RE, Hjelmeland AB, Rich JN (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15:501–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lichtman MA (2001) The stem cell in the pathogenesis and treatment of myelogenous leukemia: a perspective. Leukemia 15:1489–1494

    Article  CAS  PubMed  Google Scholar 

  • Liu SY, Zheng PS (2013) High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer. Oncotarget 4:2462–2475

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu TJ, Sun BC, Zhao XL, Zhao XM, Sun T, Gu Q, Yao Z, Dong XY, Zhao N, Liu N (2013) CD133+ cells with cancer stem cell characteristics associates with vasculogenic mimicry in triple-negative breast cancer. Oncogene 32:544–553

    Article  CAS  PubMed  Google Scholar 

  • Loebinger MR, Giangreco A, Groot KR, Prichard L, Allen K, Simpson C, Bazley L, Navani N, Tibrewal S, Davies D, Janes SM (2008) Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade. Br J Cancer 98:380–387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu H, Clauser KR, Tam WL, Fröse J, Ye X, Eaton EN, Reinhardt F, Donnenberg VS, Bhargava R, Carr SA, Weinberg RA (2014) A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages. Nat Cell Biol 16:1105–1117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, Carafa V, Spagnoli G, Terracciano L, Zlobec I (2010) Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer 103:382–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo Y, Dallaglio K, Chen Y, Robinson WA, Robinson SE, Mccarter MD, Wang J, Gonzalez R, Thompson DC, Norris DA, Roop DR, Vasiliou V, Fujita M (2012) ALDH1A isozymes are markers of human melanoma stem cells and potential therapeutic targets. Stem Cells 30:2100–2113

    Article  CAS  PubMed  Google Scholar 

  • Ma S, Chan KW, Hu L, Lee TKW, Wo JYH, Ng IOL, Zheng BJ, Guan XY (2007) Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 132:2542–2556

    Article  CAS  PubMed  Google Scholar 

  • Ma S, Chan KW, Lee TK-W, Tang KH, Wo JY-H, Zheng B-J, Guan X-Y (2008) Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol Cancer Res 6:1146–1153

    Article  CAS  PubMed  Google Scholar 

  • Mage MG, Mchugh LL, Rothstein TL (1977) Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. J Immunol Methods 15:47–56

    Article  CAS  PubMed  Google Scholar 

  • Malanchi I, Santamaria-Martínez A, Susanto E, Peng H, Lehr H-A, Delaloye J-F, Huelsken J (2012) Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481:85–89

    Article  CAS  Google Scholar 

  • Maréchal R, Demetter P, Nagy N, Berton A, Decaestecker C, Polus M, Closset J, Devière J, Salmon I, Van Laethem JL (2009) High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma. Br J Cancer 100:1444–1451

    Article  PubMed  PubMed Central  Google Scholar 

  • Maximow A (1909) Der Lymphozyt als gemeinsame Stammzelle der verschiedenen Blutelemente in der embryonalen Entwicklung und im postfetalen Leben der Säugetiere. Folia Haematologica

    Google Scholar 

  • Mazurier F, Doedens M, Gan OI, Dick JE (2003) Rapid myeloerythroid repopulation after intrafemoral transplantation of NOD-SCID mice reveals a new class of human stem cells. Nat Med 9:959–963

    Article  CAS  PubMed  Google Scholar 

  • McKenzie JL, Gan OI, Doedens M, Dick JE (2005) Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells. Blood 106:1259–1261

    Article  CAS  PubMed  Google Scholar 

  • Micucci C, Matacchione G, Valli D, Orciari S, Catalano A (2015) HIF2α is involved in the expansion of CXCR4-positive cancer stem-like cells in renal cell carcinoma. Br J Cancer 113:1178–1185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller RG, Phillips RA (1969) Separation of cells by velocity sedimentation. J Cell Physiol 73:191–201

    Article  CAS  PubMed  Google Scholar 

  • Montanaro F, Liadaki K, Schienda J, Flint A, Gussoni E, Kunkel LM (2004) Demystifying SP cell purification: viability, yield, and phenotype are defined by isolation parameters. Exp Cell Res 298:144–154

    Article  CAS  PubMed  Google Scholar 

  • Mosier DE, Gulizia RJ, Baird SM, Wilson DB (1988) Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335:256–259

    Article  CAS  PubMed  Google Scholar 

  • Murota Y, Tabu K, Taga T (2016) Requirement of ABC transporter inhibition and Hoechst 33342 dye deprivation for the assessment of side population-defined C6 glioma stem cell metabolism using fluorescent probes. BMC Cancer 16:847

    Article  PubMed  PubMed Central  Google Scholar 

  • Nassar D, Blanpain C (2016) Cancer stem cells: basic concepts and therapeutic implications. Annu Rev Pathol: Mechanisms of Disease 11:47–76

    Article  CAS  Google Scholar 

  • Nio K, Yamashita T, Okada H, Kondo M, Hayashi T, Hara Y, Nomura Y, Zeng SS, Yoshida M, Hayashi T, Sunagozaka H, Oishi N, Honda M, Kaneko S (2015) Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma. J Hepatol 63:1164–1172

    Article  CAS  PubMed  Google Scholar 

  • Nishikawa S, Konno M, Hamabe A, Hasegawa S, Kano Y, Ohta K, Fukusumi T, Sakai D, Kudo T, Haraguchi N, Satoh T, Takiguchi S, Mori M, Doki Y, Ishii H (2013) Aldehyde dehydrogenase high gastric cancer stem cells are resistant to chemotherapy. Int J Oncol 42:1437–1442

    Article  CAS  PubMed  Google Scholar 

  • Nishizawa S, Hirohashi Y, Torigoe T, Takahashi A, Tamura Y, Mori T, Kanaseki T, Kamiguchi K, Asanuma H, Morita R, Sokolovskaya A, Matsuzaki J, Yamada R, Fujii R, Kampinga HH, Kondo T, Hasegawa T, Hara I, Sato N (2012) HSP DNAJB8 controls tumor-initiating ability in renal cancer stem–like cells. Cancer Res 72:2844–2854

    Article  CAS  PubMed  Google Scholar 

  • Oates JG, Benjamin, Addla S, Samuel J, Hart C, Ramani V, Brown M, Clarke N (2009) Hoechst 33342 side population identification is a conserved and unified mechanism in urological cancers. Stem Cells Dev 18:1515–1522

    Article  CAS  PubMed  Google Scholar 

  • O'Brien CA, Kreso A, Jamieson CH (2010) Cancer stem cells and self-renewal. Clin Cancer Res 16:3113–3120

    Article  CAS  PubMed  Google Scholar 

  • O'Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110

    Article  CAS  PubMed  Google Scholar 

  • Ohkubo K, Huntenburg CC, Ohkubo K, Kurimoto S, Yokoyama MM (1984) Active T rosette formation of human T lymphocytes after stimulation with lectins. J UOEH 6:235–242

    Article  CAS  PubMed  Google Scholar 

  • Olempska M, Eisenach PA, Ammerpohl O, Ungefroren H, Fandrich F, Kalthoff H (2007) Detection of tumor stem cell markers in pancreatic carcinoma cell lines. Hepatobiliary Pancreat Dis Int 6:92–97

    CAS  PubMed  Google Scholar 

  • Opdenaker LM, Modarai SR, Boman BM (2015) The proportion of ALDEFLUOR-positive cancer stem cells changes with cell culture density due to the expression of different ALDH isoforms. Cancer Stud Mol Med 2:87–95

    Article  PubMed  PubMed Central  Google Scholar 

  • Padmanabhan R, Corsico CD, Howard TH, Holter W, Fordis CM, Willingham M, Howard BH (1988) Purification of transiently transfected cells by magnetic affinity cell sorting. Anal Biochem 170:341–348

    Article  CAS  PubMed  Google Scholar 

  • Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25:1696–1708

    Article  CAS  PubMed  Google Scholar 

  • Pearce DJ, Taussig D, Zibara K, Smith L-L, Ridler CM, Preudhomme C, Young BD, Rohatiner AZ, Lister TA, Bonnet D (2006) AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML. Blood 107:1166–1173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prieto-Vila M, Takahashi RU, Usuba W, Kohama I, Ochiya T (2017) Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci 18

    Google Scholar 

  • Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 104:973–978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ (2008) Efficient tumour formation by single human melanoma cells. Nature 456:593–598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahimi K, Füchtbauer AC, Fathi F, Mowla SJ, Füchtbauer EM (2019) Isolation of cancer stem cells by selection for miR-302 expressing cells. PeerJ 7:e6635

    Article  PubMed  PubMed Central  Google Scholar 

  • Ran D, Schubert M, Pietsch L, Taubert I, Wuchter P, Eckstein V, Bruckner T, Zoeller M, Ho AD (2009) Aldehyde dehydrogenase activity among primary leukemia cells is associated with stem cell features and correlates with adverse clinical outcomes. Exp Hematol 37:1423–1434

    Article  CAS  PubMed  Google Scholar 

  • Rasheed ZA, Yang J, Wang Q, Kowalski J, Freed I, Murter C, Hong S-M, Koorstra J-B, Rajeshkumar NV, He X, Goggins M, Iacobuzio-Donahue C, Berman DM, Laheru D, Jimeno A, Hidalgo M, Maitra A, Matsui W (2010) Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. JNCI: J Natl Cancer Inst 102:340–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren F, Sheng WQ, Du X (2013) CD133: a cancer stem cells marker, is used in colorectal cancers. World J Gastroenterol 19:2603–2611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710

    Article  CAS  PubMed  Google Scholar 

  • Ricardo S, Vieira AF, Gerhard R, Leitão D, Pinto R, Cameselle-Teijeiro JF, Milanezi F, Schmitt F, Paredes J (2011) Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype. J Clin Pathol 64:937–946

    Article  PubMed  Google Scholar 

  • Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115

    Article  CAS  PubMed  Google Scholar 

  • Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT (2004) CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 117:3539–3545

    Article  CAS  PubMed  Google Scholar 

  • Rutella S, Bonanno G, Procoli A, Mariotti A, Corallo M, Prisco MG, Eramo A, Napoletano C, Gallo D, Perillo A, Nuti M, Pierelli L, Testa U, Scambia G, Ferrandina G (2009) Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors. Clin Cancer Res 15:4299–4311

    Article  CAS  PubMed  Google Scholar 

  • Senbanjo LT, Chellaiah MA (2017) CD44: a multifunctional cell surface adhesion receptor is a regulator of progression and metastasis of cancer cells. Front Cell Dev Biol 5:18

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi C, Tian R, Wang M, Wang X, Jiang J, Zhang Z, Li X, He Z, Gong W, Qin R (2010) CD44+ CD133+ population exhibits cancer stem cell-like characteristics in human gallbladder carcinoma. Cancer Biol Ther 10:1182–1190

    Article  CAS  PubMed  Google Scholar 

  • Shi GM, Xu Y, Fan J, Zhou J, Yang XR, Qiu SJ, Liao Y, Wu WZ, Ji Y, Ke AW, Ding ZB, He YZ, Wu B, Yang GH, Qin WZ, Zhang W, Zhu J, Min ZH, Wu ZQ (2008) Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials. J Cancer Res Clin Oncol 134:1155–1163

    Article  CAS  PubMed  Google Scholar 

  • Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, St. Clair R, Baljevic M, White I, Jin DK, Chadburn A, Murphy AJ, Valenzuela DM, Gale NW, Thurston G, Yancopoulos GD, D’Angelica M, Kemeny N, Lyden D, Rafii S (2008) CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors. J Clin Invest 118:2111–2120

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shultz LD, Brehm MA, Garcia-Martinez JV, Greiner DL (2012) Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol 12:786–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sieburg HB, Cho RH, Dykstra B, Uchida N, Eaves CJ, Muller-Sieburg CE (2006) The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets. Blood 107:2311–2316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siena S, Bregni M, Brando B, Belli N, Ravagnani F, Gandola L, Stern AC, Lansdorp PM, Bonadonna G, Gianni AM (1991) Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Blood 77:400–409

    Article  CAS  PubMed  Google Scholar 

  • Silva IA, Bai S, Mclean K, Yang K, Griffith K, Thomas D, Ginestier C, Johnston C, Kueck A, Reynolds RK, Wicha MS, Buckanovich RJ (2011) Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res 71:3991–4001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh S, Brocker C, Koppaka V, Chen Y, Jackson BC, Matsumoto A, Thompson DC, Vasiliou V (2013) Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress. Free Radic Biol Med 56:89–101

    Article  CAS  PubMed  Google Scholar 

  • Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    CAS  PubMed  Google Scholar 

  • Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    Article  CAS  PubMed  Google Scholar 

  • Song W, Li H, Tao K, Li R, Song Z, Zhao Q, Zhang F, Dou K (2008) Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract 62:1212–1218

    Article  CAS  PubMed  Google Scholar 

  • Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62

    Article  CAS  PubMed  Google Scholar 

  • Srivastava VK, Nalbantoglu J (2008) Flow cytometric characterization of the DAOY medulloblastoma cell line for the cancer stem-like phenotype. Cytometry A 73:940–948

    Article  PubMed  Google Scholar 

  • van Stijn A, Van Der Pol MA, Kok A, Bontje PM, Roemen GM, Beelen RH, Ossenkoppele GJ, Schuurhuis GJ (2003) Differences between the CD34+ and CD34- blast compartments in apoptosis resistance in acute myeloid leukemia. Haematologica 88:497–508

    PubMed  Google Scholar 

  • Su J, Xu XH, Huang Q, Lu MQ, Li DJ, Xue F, Yi F, Ren JH, Wu YP (2011) Identification of cancer stem-like CD44+ cells in human nasopharyngeal carcinoma cell line. Arch Med Res 42:15–21

    Article  CAS  PubMed  Google Scholar 

  • Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H (2006) Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 351:820–824

    Article  CAS  PubMed  Google Scholar 

  • Sung JM, Cho HJ, Yi H, Lee CH, Kim HS, Kim DK, Abd El-Aty AM, Kim JS, Landowski CP, Hediger MA, Shin HC (2008) Characterization of a stem cell population in lung cancer A549 cells. Biochem Biophys Res Commun 371:163–167

    Article  CAS  PubMed  Google Scholar 

  • Suvà M-L, Riggi N, Stehle J-C, Baumer K, Tercier SP, Joseph J-M, Suvà D, Clément V, Provero P, Cironi L, Osterheld M-C, Guillou L, Stamenkovic I (2009) Identification of cancer stem cells in Ewing's sarcoma. Cancer Res 69:1776–1781

    Article  PubMed  Google Scholar 

  • Takaishi S, Okumura T, Tu S, Wang SSW, Shibata W, Vigneshwaran R, Gordon SAK, Shimada Y, Wang TC (2009) Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells 27:1006–1020

    Article  CAS  PubMed  Google Scholar 

  • Taylor MD, Poppleton H, Fuller C, Su X, Liu Y, Jensen P, Magdaleno S, Dalton J, Calabrese C, Board J, Macdonald T, Rutka J, Guha A, Gajjar A, Curran T, Gilbertson RJ (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8:323–335

    Article  CAS  PubMed  Google Scholar 

  • Terstappen LW, Safford M, Unterhalt M, Könemann S, Zurlutter K, Piechotka K, Drescher M, Aul C, Büchner T, Hiddemann W (1992) Flow cytometric characterization of acute myeloid leukemia: IV. Comparison to the differentiation pathway of normal hematopoietic progenitor cells. Leukemia 6:993–1000

    CAS  PubMed  Google Scholar 

  • Thakur R, Kumari N, Mishra DP (2021) Chapter 6—Isolation and characterization of cancer stem cells. In: Misra G, Rajawat J (eds) Protocol handbook for cancer biology. Academic Press

    Google Scholar 

  • Thakur R, Trivedi R, Rastogi N, Singh M, Mishra DP (2015) Inhibition of STAT3, FAK and Src mediated signaling reduces cancer stem cell load, tumorigenic potential and metastasis in breast cancer. Sci Rep 5:10194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Till JE, Mc CE (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14:213–222

    Article  CAS  PubMed  Google Scholar 

  • Till JE, Mcculloch EA, Siminovitch L (1964) A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells. Proc Natl Acad Sci U S A 51:29–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tirino V, Desiderio V, D'aquino R, De Francesco F, Pirozzi G, Galderisi U, Cavaliere C, De Rosa A, Papaccio G (2008) Detection and characterization of CD133+ cancer stem cells in human solid tumours. PLoS One 3:e3469

    Article  PubMed  PubMed Central  Google Scholar 

  • Uckun FM, Sather H, Reaman G, Shuster J, Land V, Trigg M, Gunther R, Chelstrom L, Bleyer A, Gaynon P et al (1995) Leukemic cell growth in SCID mice as a predictor of relapse in high-risk B-lineage acute lymphoblastic leukemia. Blood 85:873–878

    Article  CAS  PubMed  Google Scholar 

  • Visser JW, Bol SJ, Van Den Engh G (1981) Characterization and enrichment of murine hemopoietic stem cells by fluorescence activated cell sorting. Exp Hematol 9:644–655

    CAS  PubMed  Google Scholar 

  • Vormoor J, Lapidot T, Pflumio F, Risdon G, Patterson B, Broxmeyer H, Dick J (1994) Immature human cord blood progenitors engraft and proliferate to high levels in severe combined immunodeficient mice. Blood 83:2489–2497

    Article  CAS  PubMed  Google Scholar 

  • Wan G, Zhou L, Xie M, Chen H, Tian J (2010) Characterization of side population cells from laryngeal cancer cell lines. Head Neck 32:1302–1309

    Article  PubMed  Google Scholar 

  • Wang L, Park P, Zhang H, La Marca F, Lin C-Y (2011) Prospective identification of tumorigenic osteosarcoma cancer stem cells in OS99-1 cells based on high aldehyde dehydrogenase activity. Int J Cancer 128:294–303

    Article  CAS  PubMed  Google Scholar 

  • Wei X, Dombkowski D, Meirelles K, Pieretti-Vanmarcke R, Szotek PP, Chang HL, Preffer FI, Mueller PR, Teixeira J, Maclaughlin DT, Donahoe PK (2010) Mullerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics. Proc Natl Acad Sci U S A 107:18874–18879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wenqi D, Li W, Shanshan C, Bei C, Yafei Z, Feihu B, Jie L, Daiming F (2009) EpCAM is overexpressed in gastric cancer and its downregulation suppresses proliferation of gastric cancer. J Cancer Res Clin Oncol 135:1277–1285

    Article  PubMed  Google Scholar 

  • Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV, Varticovski L (2008) Brca1 breast tumors contain distinct CD44+/CD24- and CD133+cells with cancer stem cell characteristics. Breast Cancer Res 10:R10

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu A, Luo W, Zhang Q, Yang Z, Zhang G, Li S, Yao K (2013) Aldehyde dehydrogenase 1, a functional marker for identifying cancer stem cells in human nasopharyngeal carcinoma. Cancer Lett 330:181–189

    Article  CAS  PubMed  Google Scholar 

  • Wuputra K, Ku C-C, Kato K, Wu D-C, Saito S, Yokoyama KK (2021) Translational models of 3-D organoids and cancer stem cells in gastric cancer research. Stem Cell Res Ther 12:492

    Article  PubMed  PubMed Central  Google Scholar 

  • Xiao W, Gao Z, Duan Y, Yuan W, Ke Y (2017) Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma. J Exp Clin Cancer Res 36:41

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu R, Cai MY, Luo RZ, Tian X, Han JD, Chen MK (2016) The expression status and prognostic value of cancer stem cell biomarker CD133 in cutaneous squamous cell carcinoma. JAMA Dermatol 152:305–311

    Article  PubMed  Google Scholar 

  • Xue Z, Yan H, Li J, Liang S, Cai X, Chen X, Wu Q, Gao L, Wu K, Nie Y, Fan D (2012) Identification of cancer stem cells in vincristine preconditioned SGC7901 gastric cancer cell line. J Cell Biochem 113:302–312

    Article  CAS  PubMed  Google Scholar 

  • Yang CH, Wang HL, Lin YS, Kumar KP, Lin HC, Chang CJ, Lu CC, Huang TT, Martel J, Ojcius DM, Chang YS, Young JD, Lai HC (2014) Identification of CD24 as a cancer stem cell marker in human nasopharyngeal carcinoma. PLoS One 9:e99412

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang L, Shi P, Zhao G, Xu J, Peng W, Zhang J, Zhang G, Wang X, Dong Z, Chen F, Cui H (2020) Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther 5:8

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang M, Zhang R, Yan M, Ye Z, Liang W, Luo Z (2010) Detection and characterization of side population in Ewing's sarcoma SK-ES-1 cells in vitro. Biochem Biophys Res Commun 391:1062–1066

    Article  CAS  PubMed  Google Scholar 

  • Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, Chu PWK, Lam CT, Poon RTP, Fan ST (2008) Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 13:153–166

    Article  CAS  PubMed  Google Scholar 

  • Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012

    Article  CAS  PubMed  Google Scholar 

  • Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL, Black KL, Yu JS (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23:9392–9400

    Article  CAS  PubMed  Google Scholar 

  • Zhan HX, Xu JW, Wu D, Zhang TP, Hu SY (2015) Pancreatic cancer stem cells: new insight into a stubborn disease. Cancer Lett 357:429–437

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Yang S, He YJ, Shao HY, Wang L, Chen H, Gao YJ, Qing FX, Chen XC, Zhao LY, Tan S (2010) Fluorouracil selectively enriches stem-like leukemic cells in a leukemic cell line. Int J Biol Sci 6:419–427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang P, Zhang Y, Mao L, Zhang Z, Chen W (2009) Side population in oral squamous cell carcinoma possesses tumor stem cell phenotypes. Cancer Lett 277:227–234

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68:4311–4320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Sun B, Zhao X, Liu Z, Wang X, Yao X, Dong X, Chi J (2013) Clinical significances and prognostic value of cancer stem-like cells markers and vasculogenic mimicry in renal cell carcinoma. J Surg Oncol 108:414–419

    Article  CAS  PubMed  Google Scholar 

  • Zhou L, Wei X, Cheng L, Tian J, Jiang JJ (2007) CD133, one of the markers of cancer stem cells in Hep-2 cell line. Laryngoscope 117:455–460

    Article  CAS  PubMed  Google Scholar 

  • Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7:1028–1034

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Yu J, Wang S, Lu R, Wu J, Jiang B (2014) Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells. Oncol Rep 32:2437–2444

    Article  CAS  PubMed  Google Scholar 

  • Zhu Z, Hao X, Yan M, Yao M, Ge C, Gu J, Li J (2010) Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer 126:2067–2078

    CAS  PubMed  Google Scholar 

  • Zhuang HW, Mo TT, Hou WJ, Xiong GX, Zhu XL, Fu QL, Wen WP (2013) Biological characteristics of CD133(+) cells in nasopharyngeal carcinoma. Oncol Rep 30:57–63

    Article  PubMed  PubMed Central  Google Scholar 

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Author Contributions

Conceptualization, F.I., J.M.; literature investigation, J.M.; Tables, J.M.; original manuscript preparation, J.M.; review and editing, F.I., J.M. All authors have read and agreed to the published version of the manuscript.

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  1. School of Medicine and Dentistry, Griffith University, Gold Coast, QLD, Australia

    Jeremy Martin

  2. Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh

    Farhadul Islam

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  1. Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh

    Farhadul Islam

  2. School of Medicine and Dentistry, Griffith University, Gold Coast, QLD, Australia

    Alfred K. Lam

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Martin, J., Islam, F. (2023). Detection and Isolation of Cancer Stem Cells. In: Islam, F., Lam, A.K. (eds) Cancer Stem Cells: Basic Concept and Therapeutic Implications. Springer, Singapore. https://doi.org/10.1007/978-981-99-3185-9_3

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