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[1]MR Junttila and FJ de Sauvage. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501(7467):346-54 (2013)
[2]Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine 7:730-737 (1997)
[3]Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–8 (2003)
[4]Colak S and Medema JP. Cancer stem cells – important players in tumor therapy Resistance FEBS Journal 281:4779–4791 (2014)
[5]Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors (RECIST Guidelines). J Natl Cancer Inst 2000;92:205–16 (2000)
[6]Chen J, Li Y, Yu T-S, McKay RM, Burns DK, Kernie SG, Parada LF. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature;488:522–6 (2012)
[7]Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, Clevers H. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337:730–735 (2012)
[8]Driessens G, Beck B, Caauwe A, Simons BD, Blanpain C. Defining the mode of tumour growth by clonal analysis. Nature 488:527–530 (2012)
[9]Mukherjee S, Kong J, Brat DJ. Cancer stem cell division: when the rules of asymmetry are broken. Stem Cells Dev 24(4):405-16 (2015)
[10]Vidal SJ, Rodriguez-Bravo V, Galsky M, Cordon-Cardo C, Domingo-Domenech J.Oncogene 4;33(36):4451-63 (2014)
[11]Valent 1, Bonnet D, De Maria R, Lapidot T, Copland M, Melo JV, Chomienne C, Ishikawa F, Schuringa JJ, Stassi G, Huntly B, Herrmann H, Soulier J, Roesch A, Schuurhuis GJ, Wöhrer S, Arock M, Zuber J, Cerny-Reiterer S, Johnsen HE, Andreeff M, Eaves C. Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer 12(11):767-75 (2012)
[12]Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183(4):1797-806 (1996)
[13]Wu C, Alman BA. Side population cells in human cancers. Cancer Lett 268(1):1-9 (2008)
[14]Shapiro, A.B and Ling, V. Reconstitution of drug transport bypurified P-glycoprotein, J Bid Chem 270, 16167-75 (1995)
[15]Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP. 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(9):1028-34 (2001)
[16]Loebinger MR, Giangreco A, Groot KR, Prichard L, Allen K, Simpson C, Bazley L, Navani N, Tibrewal S, Davies D, Janes SM. Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade. Br J Cancer 98(2):380-7 (2008)
[17]SP Hong, J Wen, S Bang, S Park, and SY Song. CD44-positive cells are responsible for gemcitabine resistance in pancreatic cancer cells. Int J of Cancer 125(10):2323-2331 (2009)
[18]Mathews, LA, Cabarcas, SM, Hurt, EM (Eds). DNA Repair of Cancer Stem Cells. Springer
[19]Cojoc M, Mäbert K1, Muders MH2, Dubrovska A. A role for cancer stem cells in therapy resistance: Cellular and molecular mechanisms. Semin Cancer Biol (2014, In Press)
[20]Bartucci M, Svensson S, Romania P, Dattilo R, Patrizii M, Signore M, et al. Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy. Cell Death Differ 19 (5):768–78 (2012)
[21]Yin H, Glass J. The phenotypic radiation resistance of CD44+/CD24(-or low)breast cancer cells is mediated through the enhanced activation of ATM signaling. PLoS ONE 6(9):e24080 (2011)
[22]Richichi C, Brescia P, Alberizzi V, Fornasar Li, Pelicci G. Marker-independent Method for Isolating Slow-Dividing Cancer Stem Cells in Human Glioblastoma. Neoplasia 15(7): 840–7 (2013)
[23]Ni C, Wu P, Zhu X, Ye J, Zhang Z, Chen Z, Zhang T, Zhang T, Wang K, Wu D, Qiu F, Huang J. IFN-γ selectively exerts pro-apoptotic effects on tumor-initiating label-retaining colon cancer cells. Cancer Lett.;336(1):174-84 (2013)
[24]Kusumbe AP, Bapat SA. Cancer stem cells and aneuploid populations within developing tumors are the major determinants of tumor dormancy. Cancer Res 69(24):9245-53 (2009)
[25]Dembinski JL, Krauss S. Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma. Clin Exp Metastasis 26(7):611-23 (2009)
[26]Vanner RJ, Remke M, Gallo M, Selvadurai HJ, Coutinho F, Lee L, Kushida M, Head R, Morrissy S, Zhu X, Aviv T, Voisin V, Clarke ID, Li Y, Mungall AJ, Moore RA, Ma Y, Jones SJM, Marra MA, Malkin D, Northcott PA, Kool M, Pfister SM, Bader G, Hochedlinger K, Korshunov A, Taylor MD, Dirks PB. Quiescent Sox2+ Cells Drive Hierarchical Growth and Relapse in Sonic Hedgehog Subgroup Medulloblastoma. Cancer Cell 26(1): 33-47 (2014)
[27]Xue Z, Yan H, Li J, Liang S, Cai X, Chen X, Wu Q, Gao L, Wu K, Nie Y, Fan D. Identification of cancer stem cells in vincristine preconditioned SGC7901 gastric cancer cell line. J Cell Biochem 113(1):302-12 (2012)
[28]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. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555-67 (2007)
[29]Ricardo S, Vieira AF, Gerhard R, Leita˜o D, Pinto R, Cameselle-Teijeiro JF, Milanezi F, Schmitt F, Paredes J. Breast cancer stem cell markers CD44, CD24 andALDH1: expression distribution within intrinsic molecular subtype. J Clin Pathol 64:937e946 (2011)
[30]Charafe-Jauffret E, Ginestier C, Iovino F, Tarpin C, Diebel M, Esterni B, Houvenaeghel G, Extra JM, Bertucci F, Jacquemier J, Xerri L, Dontu G, Stassi G, Xiao Y, Barsky SH, Birnbaum D, Viens P, Wicha MS. Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res 16(1):45-55 (2010)
[31]Zeppernick F, Ahmadi R, Campos B, Dictus C, Helmke BM, Becker N, Engel F, Acker T, Momma S, Herold-Mende C, Lichter P, Radlwimmer B, Goidts V. Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res 14:123–129 (2008)
[32]Zhang M, Song T, Yang L, Chen R, Wu L, Yang Z, Fang J. Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma. J Exp Clin Cancer Res 27:85. (2008)
[33]Coco C, Zannoni GF, Caredda E, Sioletic S, Boninsegna A, Migaldi M, Rizzo G, Bonetti LR, Genovese G, Stigliano E, Cittadini A, Sgambato A. Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients. J Exp Clin Cancer Res 31:71 (2012)
[34]Wan F, Herold-Mende C, Campos B, Centner FS, Dictus C, Becker N, Devens F, Mogler C, Felsberg J, Grabe N, Reifenberger G, Lichter P, Unterberg A, Bermejo JL, Ahmadi R. Association of stem cell-related markers and survival in astrocytic gliomas. Biomarkers 16:136–143 (2011)
[35]Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B, van Galen P, Metzeler KH, Poeppl A, Ling V, Beyene J, Canty AJ, Danska JS, Bohlander SK, Buske C, Minden MD, Golub TR, Jurisica I, Ebert BL, Dick JE. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 17(9):1086-93 (2011)
[36]Hurt EM, Farrar WL. Cancer Stem Cells: The Seeds of Metastasis? Mol Interventions 8(3): 140-42 (2008)
[37]Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704-15 (2008)
[38]Theodoropoulos PA, Polioudaki H, Agelaki S, Kallergi G, Saridaki Z, Mavroudis D, Georgoulias V. Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer. Cancer Lett 288(1):99-106 (2010)
[39]Pirozzi G, Tirino V, Camerlingo R, La Rocca A, Martucci N, Scognamiglio G, Franco R, Cantile M, Normanno N, Rocco G. Prognostic value of cancer stem cells, epithelial-mesenchymal transition and circulating tumor cells in lung cancer. Oncol Rep 29(5):1763-8 (2013)
[40]Kantara C, O’Connell MR, Luthra G, Gajjar A, Sarkar S, Ullrich RL, Singh P. Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach for diagnosis of colon cancer relapse/metastasis. Lab Invest 95(1):100-12 (2015)
[41]Zhu L, Zhang W, Wang J, Liu R. Evidence of CD90+CXCR4+ cells as circulating tumor stem cells in hepatocellular carcinoma. Tumour Biol (2015)
[42]Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, Klein C, Saini M, Bäuerle T, Wallwiener M, Holland-Letz T, Höfner T, Sprick M, Scharpff M, Marmé F, Sinn HP, Pantel K, Weichert W, Trumpp A. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31(6):539-44 (2013)
[43]Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG, Trapani F, Polanski R, Burt DJ, Simpson KL, Morris K, Pepper SD, Nonaka D, Greystoke A, Kelly P, Bola B, Krebs MG, Antonello J, Ayub M, Faulkner S, Priest L, Carter L, Tate C, Miller CJ, Blackhall F, Brady G, Dive C. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat Med 20(8):897-903 (2014)
[44]Cayrefourcq L, Mazard T, Joosse S, Solassol J, Ramos J, Assenat E, Schumacher U, Costes V, Maudelonde T, Pantel K, Alix-Panabières C. Establishment and Characterization of a Cell Line from Human Circulating Colon Cancer Cells. Cancer Res 75(5):892-901 (2015)
[45]Klaus Pantel, Ruud H. Brakenhoff and Burkhard Brandt. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nature Rev Cancer 8, 329-340 (2008)
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[49]Cabrera MC, Hollingsworth RE, Hurt EM. Cancer stem cell plasticity and tumor hierarchy. World J Stem Cells 7(1):27-36 (2015)
[50]Schott AF, Landis MD, Dontu G, Griffith KA, Layman RM, Krop I, Paskett LA, Wong H, Dobrolecki LE, Lewis MT, Froehlich AM, Paranilam J, Hayes DF, Wicha MS, Chang JC. Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors. Clin Cancer Res 19(6):1512-24 (2013)
[51]Weller P, Nel I, Hassenkamp P, Gauler T, Schlueter A, Lang S, Dountsop P, Hoffmann AC, Lehnerdt G. Detection of circulating tumor cell subpopulations in patients with head and neck squamous cell carcinoma (HNSCC). PLoS One 9(12):e113706 (2014)
[52]Katoh S, Goi T, Naruse T, Ueda Y, Kurebayashi H, Nakazawa T, Kimura Y, Hirono Y, Yamaguchi A. Cancer Stem Cell Marker in Circulating Tumor Cells: Expression of CD44 Variant Exon 9 Is Strongly Correlated to Treatment Refractoriness, Recurrence and Prognosis of Human Colorectal Cancer. Anticancer Res 35(1):239-44 (2015)
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[57]Vidal SJ, Rodriguez-Bravo V, Galsky M, Cordon-Cardo C and Domingo-Domenech J. Targeting cancer stem cells to suppress acquired chemotherapy resistance. Oncogene 33, 4451–4463 (2014)
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Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Will cancer stem cells provide more effective biomarkers?
1 Oncology Research, Medimmune, LLC. One MedImmune Way, Gaithersburg, MD 20878
*Author to whom correspondence should be addressed.
Abstract
Cancer stem cells (CSCs) represent a rare subpopulation of tumor cells responsible for tumor initiation and eventual patient relapse. Strong preclinical evidence points to the importance of this population for therapeutic intervention and currently there are several anti-CSC therapies under development. While we begin to advance these therapies into the clinic, there is a need to develop biomarkers to measure both patient response and prognosis. This review will discuss the experimental evidence for the role of CSCs in patient outcomes as well as the need, challenges and the hope that CSC biomarkers may provide.
Keywords
- Cancer
- Stem Cells
- Biomarkers
- Review
References
- [1] MR Junttila and FJ de Sauvage. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501(7467):346-54 (2013)
- [2] Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine 7:730-737 (1997)
- [3] Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–8 (2003)
- [4] Colak S and Medema JP. Cancer stem cells – important players in tumor therapy Resistance FEBS Journal 281:4779–4791 (2014)
- [5] Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors (RECIST Guidelines). J Natl Cancer Inst 2000;92:205–16 (2000)
- [6] Chen J, Li Y, Yu T-S, McKay RM, Burns DK, Kernie SG, Parada LF. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature;488:522–6 (2012)
- [7] Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, Clevers H. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337:730–735 (2012)
- [8] Driessens G, Beck B, Caauwe A, Simons BD, Blanpain C. Defining the mode of tumour growth by clonal analysis. Nature 488:527–530 (2012)
- [9] Mukherjee S, Kong J, Brat DJ. Cancer stem cell division: when the rules of asymmetry are broken. Stem Cells Dev 24(4):405-16 (2015)
- [10] Vidal SJ, Rodriguez-Bravo V, Galsky M, Cordon-Cardo C, Domingo-Domenech J.Oncogene 4;33(36):4451-63 (2014)
- [11] Valent 1, Bonnet D, De Maria R, Lapidot T, Copland M, Melo JV, Chomienne C, Ishikawa F, Schuringa JJ, Stassi G, Huntly B, Herrmann H, Soulier J, Roesch A, Schuurhuis GJ, Wöhrer S, Arock M, Zuber J, Cerny-Reiterer S, Johnsen HE, Andreeff M, Eaves C. Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer 12(11):767-75 (2012)
- [12] Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183(4):1797-806 (1996)
- [13] Wu C, Alman BA. Side population cells in human cancers. Cancer Lett 268(1):1-9 (2008)
- [14] Shapiro, A.B and Ling, V. Reconstitution of drug transport bypurified P-glycoprotein, J Bid Chem 270, 16167-75 (1995)
- [15] Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP. 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(9):1028-34 (2001)
- [16] Loebinger MR, Giangreco A, Groot KR, Prichard L, Allen K, Simpson C, Bazley L, Navani N, Tibrewal S, Davies D, Janes SM. Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade. Br J Cancer 98(2):380-7 (2008)
- [17] SP Hong, J Wen, S Bang, S Park, and SY Song. CD44-positive cells are responsible for gemcitabine resistance in pancreatic cancer cells. Int J of Cancer 125(10):2323-2331 (2009)
- [18] Mathews, LA, Cabarcas, SM, Hurt, EM (Eds). DNA Repair of Cancer Stem Cells. Springer
- [19] Cojoc M, Mäbert K1, Muders MH2, Dubrovska A. A role for cancer stem cells in therapy resistance: Cellular and molecular mechanisms. Semin Cancer Biol (2014, In Press)
- [20] Bartucci M, Svensson S, Romania P, Dattilo R, Patrizii M, Signore M, et al. Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy. Cell Death Differ 19 (5):768–78 (2012)
- [21] Yin H, Glass J. The phenotypic radiation resistance of CD44+/CD24(-or low)breast cancer cells is mediated through the enhanced activation of ATM signaling. PLoS ONE 6(9):e24080 (2011)
- [22] Richichi C, Brescia P, Alberizzi V, Fornasar Li, Pelicci G. Marker-independent Method for Isolating Slow-Dividing Cancer Stem Cells in Human Glioblastoma. Neoplasia 15(7): 840–7 (2013)
- [23] Ni C, Wu P, Zhu X, Ye J, Zhang Z, Chen Z, Zhang T, Zhang T, Wang K, Wu D, Qiu F, Huang J. IFN-γ selectively exerts pro-apoptotic effects on tumor-initiating label-retaining colon cancer cells. Cancer Lett.;336(1):174-84 (2013)
- [24] Kusumbe AP, Bapat SA. Cancer stem cells and aneuploid populations within developing tumors are the major determinants of tumor dormancy. Cancer Res 69(24):9245-53 (2009)
- [25] Dembinski JL, Krauss S. Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma. Clin Exp Metastasis 26(7):611-23 (2009)
- [26] Vanner RJ, Remke M, Gallo M, Selvadurai HJ, Coutinho F, Lee L, Kushida M, Head R, Morrissy S, Zhu X, Aviv T, Voisin V, Clarke ID, Li Y, Mungall AJ, Moore RA, Ma Y, Jones SJM, Marra MA, Malkin D, Northcott PA, Kool M, Pfister SM, Bader G, Hochedlinger K, Korshunov A, Taylor MD, Dirks PB. Quiescent Sox2+ Cells Drive Hierarchical Growth and Relapse in Sonic Hedgehog Subgroup Medulloblastoma. Cancer Cell 26(1): 33-47 (2014)
- [27] Xue Z, Yan H, Li J, Liang S, Cai X, Chen X, Wu Q, Gao L, Wu K, Nie Y, Fan D. Identification of cancer stem cells in vincristine preconditioned SGC7901 gastric cancer cell line. J Cell Biochem 113(1):302-12 (2012)
- [28] 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. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555-67 (2007)
- [29] Ricardo S, Vieira AF, Gerhard R, Leita˜o D, Pinto R, Cameselle-Teijeiro JF, Milanezi F, Schmitt F, Paredes J. Breast cancer stem cell markers CD44, CD24 andALDH1: expression distribution within intrinsic molecular subtype. J Clin Pathol 64:937e946 (2011)
- [30] Charafe-Jauffret E, Ginestier C, Iovino F, Tarpin C, Diebel M, Esterni B, Houvenaeghel G, Extra JM, Bertucci F, Jacquemier J, Xerri L, Dontu G, Stassi G, Xiao Y, Barsky SH, Birnbaum D, Viens P, Wicha MS. Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res 16(1):45-55 (2010)
- [31] Zeppernick F, Ahmadi R, Campos B, Dictus C, Helmke BM, Becker N, Engel F, Acker T, Momma S, Herold-Mende C, Lichter P, Radlwimmer B, Goidts V. Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res 14:123–129 (2008)
- [32] Zhang M, Song T, Yang L, Chen R, Wu L, Yang Z, Fang J. Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma. J Exp Clin Cancer Res 27:85. (2008)
- [33] Coco C, Zannoni GF, Caredda E, Sioletic S, Boninsegna A, Migaldi M, Rizzo G, Bonetti LR, Genovese G, Stigliano E, Cittadini A, Sgambato A. Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients. J Exp Clin Cancer Res 31:71 (2012)
- [34] Wan F, Herold-Mende C, Campos B, Centner FS, Dictus C, Becker N, Devens F, Mogler C, Felsberg J, Grabe N, Reifenberger G, Lichter P, Unterberg A, Bermejo JL, Ahmadi R. Association of stem cell-related markers and survival in astrocytic gliomas. Biomarkers 16:136–143 (2011)
- [35] Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B, van Galen P, Metzeler KH, Poeppl A, Ling V, Beyene J, Canty AJ, Danska JS, Bohlander SK, Buske C, Minden MD, Golub TR, Jurisica I, Ebert BL, Dick JE. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 17(9):1086-93 (2011)
- [36] Hurt EM, Farrar WL. Cancer Stem Cells: The Seeds of Metastasis? Mol Interventions 8(3): 140-42 (2008)
- [37] Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704-15 (2008)
- [38] Theodoropoulos PA, Polioudaki H, Agelaki S, Kallergi G, Saridaki Z, Mavroudis D, Georgoulias V. Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer. Cancer Lett 288(1):99-106 (2010)
- [39] Pirozzi G, Tirino V, Camerlingo R, La Rocca A, Martucci N, Scognamiglio G, Franco R, Cantile M, Normanno N, Rocco G. Prognostic value of cancer stem cells, epithelial-mesenchymal transition and circulating tumor cells in lung cancer. Oncol Rep 29(5):1763-8 (2013)
- [40] Kantara C, O’Connell MR, Luthra G, Gajjar A, Sarkar S, Ullrich RL, Singh P. Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach for diagnosis of colon cancer relapse/metastasis. Lab Invest 95(1):100-12 (2015)
- [41] Zhu L, Zhang W, Wang J, Liu R. Evidence of CD90+CXCR4+ cells as circulating tumor stem cells in hepatocellular carcinoma. Tumour Biol (2015)
- [42] Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, Klein C, Saini M, Bäuerle T, Wallwiener M, Holland-Letz T, Höfner T, Sprick M, Scharpff M, Marmé F, Sinn HP, Pantel K, Weichert W, Trumpp A. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31(6):539-44 (2013)
- [43] Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG, Trapani F, Polanski R, Burt DJ, Simpson KL, Morris K, Pepper SD, Nonaka D, Greystoke A, Kelly P, Bola B, Krebs MG, Antonello J, Ayub M, Faulkner S, Priest L, Carter L, Tate C, Miller CJ, Blackhall F, Brady G, Dive C. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat Med 20(8):897-903 (2014)
- [44] Cayrefourcq L, Mazard T, Joosse S, Solassol J, Ramos J, Assenat E, Schumacher U, Costes V, Maudelonde T, Pantel K, Alix-Panabières C. Establishment and Characterization of a Cell Line from Human Circulating Colon Cancer Cells. Cancer Res 75(5):892-901 (2015)
- [45] Klaus Pantel, Ruud H. Brakenhoff and Burkhard Brandt. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nature Rev Cancer 8, 329-340 (2008)
- [46] Grover PK, Cummins AG, Price TJ, Roberts-Thomson IC, Hardingham JE. Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research. Annals of Oncology 25(8):1506-16 (2014)
- [47] Esmaeilsabzali H, Beischlag TV, Cox ME, Parameswaran AM, Park EJ. Detection and isolation of circulating tumor cells: principles and methods. Biotechnol Adv 31(7):1063-84 (2013)
- [48] Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH and Dive C. Molecular analysis of circulating tumour cells—biology and biomarkers. Nature Reviews Clinical Oncology 11, 129–144 (2014)
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