Advertisement

Role of Cancer Stem Cells of Breast, Colon, and Melanoma Tumors in the Response to Antitumor Therapy

  • Juan Antonio Marchal
  • María Angel García
  • Houria Boulaiz
  • Macarena Perán
  • Pablo Álvarez
  • José Carlos Prados
  • Consolación Melguizo
  • Antonia Aránega
Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 3)

Abstract

Solid tumors represent the major cancer burden, and epithelial cancers arising in tissues that include breast, colon and skin constitute the most common forms of all cancers and display extraordinarily high mortality rates in industrialized countries. Recent data suggest that cancers arise from rare self-renewing stem cells that are biologically distinct from their more numerous differentiated progeny. Growing evidence suggests that pathways regulating normal stem cell self-renewal and differentiation are also present in cancer cells and cancer stem cells (CSCs) in solid tumors. A small number of cells identified as CSCs from solid tumors usually express organ-specific markers, contribute to chemotherapy resistance and are able to generate a new tumor in immunodeficient mice. Although in recent years the knowledge of the biology of CSCs in these tumors has increased, however, we are not yet able to clearly distinguish between the characteristics of those with compared with non-tumor stem cells, or even to set up a CSCs methodology of isolation. It becomes necessary, therefore, further evaluation of CSCs biomarkers and a better understanding of signaling pathways that support stem cell renewal in normal and malignant tissue. Actually, the isolation and characterization of CSCs in breast, colon and melanoma tumor is providing a great aid in the diagnosis, prediction of prognosis and response to chemotherapy. Moreover, the discovery and development of specific therapies that target CSCs has the potential to revolutionize the treatment of these tumors.

Keywords

Breast Colon Melanoma Tumors CSCs Oncogene 

References

  1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988PubMedCrossRefGoogle Scholar
  2. Barker N, Van Es J, Kuipers J, Kujala P, Van Den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–1007PubMedCrossRefGoogle Scholar
  3. Boiko AD, Razorenova OV, Van de Rijn M, Swetter SM, Jonson DL, Ly DP, Butler PD, Yang GP, Joshua B, Kaplan MJ, Longaker MT, Weissman IL (2010) Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271. Nature 466:133–137PubMedCrossRefGoogle Scholar
  4. Cariati M, Naderi A, Brown JP, Smalley MJ, Pinder SE, Caldas C (2008) Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line. Int J Cancer 122:298–304PubMedCrossRefGoogle Scholar
  5. Cheli Y, Guiliano S, Botton T, Rocchi S, Hofman V, Hofman P, Bahadoran P, Bertolotto C, Ballotti R (2011) Mitf is the key molecular switch between mouse or human melanoma initiating cells and their differentiated progeny. Oncogene. [Epub ahead of print]Google Scholar
  6. Chikazawa N, Tanaka H, Tasaka T, Nakamura M, Tanaka M, Onishi H, Katano M (2010) Inhibition of Wnt signaling pathway decreases chemotherapy-resistant side-population colon cancer cells. Anticancer Res 30:2041–2048PubMedGoogle Scholar
  7. Clayton H, Titley I, Vivanco M (2004) Growth and differentiation of progenitor/stem cells derived from the human mammary gland. Exp Cell Res 297:444–460PubMedCrossRefGoogle Scholar
  8. 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 USA 104:10158–10163PubMedCrossRefGoogle Scholar
  9. Elsaba TM, Martinez-Pomares L, Robins AR, Crook S, Seth R, Jackson D, McCart A, Silver AR, Tomlinson IP, Ilyas M (2010) The stem cell marker CD133 associates with enhanced colony formation and cell motility in colorectal cancer. PLoS One 5:e10714PubMedCrossRefGoogle Scholar
  10. Fabrizi E, di Martino S, Pelacchi F, Ricci-Vitiani L (2010) Therapeutic implications of colon cancer stem cells. World J Gastroenterol 16:3871–3877PubMedCrossRefGoogle Scholar
  11. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65:9328–9337PubMedCrossRefGoogle Scholar
  12. Frank NY, Margaryan A, Huang Y, Schatton T, Waaga-Gasser AM, Gasser M, Sayegh MH, Sadee W, Frank MH (2005) ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res 65:4320–4333PubMedCrossRefGoogle Scholar
  13. 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 1:555–567PubMedCrossRefGoogle Scholar
  14. Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138:645–659PubMedCrossRefGoogle Scholar
  15. Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, Bundred NJ, Clarke RB (2010) Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res 70:709–718PubMedCrossRefGoogle Scholar
  16. Held MA, Curley DP, Dankort D, McMahon M, Muthusamy V, Bosenberg MW (2010) Characterization of melanoma cells capable of propagating tumors from a single cell. Cancer Res 70:388–397PubMedCrossRefGoogle Scholar
  17. Hoek KS, Eichhoff OM, Schlegel NC, Döbbeling U, Kobert N, Schaerer L, Hemmi S, Dummer R (2008) In vivo switching of human melanoma cells between proliferative and invasive states. Cancer Res 68:650–656PubMedCrossRefGoogle Scholar
  18. 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 69:3382–3389PubMedCrossRefGoogle Scholar
  19. Kanwar SS, Yu Y, Nautiyal J, Patel BB, Majumdar AP (2010) The Wnt/beta-catenin pathway regulates growth and maintenance of colonospheres. Mol Cancer 9:212PubMedCrossRefGoogle Scholar
  20. Keysar SB, Jimeno A (2010) More than markers: biological significance of cancer stem cell-defining molecules. Mol Cancer Ther 9:2450–2457PubMedCrossRefGoogle Scholar
  21. Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, Clouthier SG, Wicha MS (2009) Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol 7:e1000121PubMedCrossRefGoogle Scholar
  22. Kupas V, Weishaupt C, Siepmann D, Kaserer ML, Eickelmann M, Metze D, Luger TA, Beissert S, Loser K (2011) RANK is expressed in metastatic melanoma and highly upregulated on melanoma-initiating cells. J Invest Dermatol 131:944–955PubMedCrossRefGoogle Scholar
  23. Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, Suri P, Wicha MS (2006) Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 66:6063–6071PubMedCrossRefGoogle Scholar
  24. Marcato P, Dean CA, Giacomantonio CA, Lee PW (2009) Oncolytic reovirus effectively targets breast cancer stem cells. Mol Ther 17:972–979PubMedCrossRefGoogle Scholar
  25. Marchal JA, Boulaiz H, Prados J, Campos J, González F, Melguizo C, Velez C, Perán M, Carrillo E, Rodríguez F, Hita F, Ortiz R, Martínez-Amat A, Caba O, Ventura C, Aránega A (2009) Therapeutic potential of differentiation in cancer and normal stem cells. In: Marchal JA et al (eds). Nova Science Publishers, New York, pp 1–116Google Scholar
  26. Monzani E, Facchetti F, Galmozzi E, Corsini E, Benetti A, Cavazzin C, Gritti A, Piccinini A, Porro D, Santinami M, Invernici G, Parati E, Alessandri G, La Porta CA (2007) Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur J Cancer 43:935–946PubMedCrossRefGoogle Scholar
  27. Murayama M, Okamoto R, Tsuchiya K, Akiyama J, Nakamura T, Sakamoto N, Kanai T, Watanabe M (2009) Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells. J Gastroenterol 44:173–182PubMedCrossRefGoogle Scholar
  28. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110PubMedCrossRefGoogle Scholar
  29. Oberneder R, Weckermann D, Ebner B, Quadt C, Kirchinger P, Raum T, Locher M, Prang N, Baeuerle PA, Leo E (2006) A phase I study with adecatumumab, a human antibody directed against epithelial cell adhesion molecule, in hormone refractory prostate cancer patients. Eur J Cancer 42:2530–2538PubMedCrossRefGoogle Scholar
  30. Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG (2005) Side population is enriched in tumorigenic, stemlike cancer cells, whereas ABCG2+ and A. Cancer Res 65:6207–6219PubMedCrossRefGoogle Scholar
  31. Phillips TM, McBride WH, Pajonk F (2006) The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst 98:1777–1785PubMedCrossRefGoogle Scholar
  32. Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ (2008) Efficient tumour formation by single human melanoma cells. Nature 456:593–598PubMedCrossRefGoogle Scholar
  33. Quintana E, Shackleton M, Foster HR, Fullen DR, Sabel MS, Johnson TM, Morrison SJ (2010) Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized. Cancer Cell 18:510–523PubMedCrossRefGoogle Scholar
  34. Rappa G, Fodstad O, Lorico A (2008) The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma. Stem Cells 26:3008–3017PubMedCrossRefGoogle Scholar
  35. Reedijk M, Odorcic S, Zhang H, Chetty R, Tennert C, Dickson BC, Lockwood G, Gallinger S, Egan SE (2008) Activation of Notch signaling in human colon adenocarcinoma. Int J Oncol 33:1223–1229PubMedGoogle Scholar
  36. Ricci-Vitiani L, Lombardi D, Pilozzi E, Biffoni M, Todaro M, and Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115PubMedCrossRefGoogle Scholar
  37. Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, Vultur A, Basu D, Gimotty P, Vogt T, Herlyn M (2010) A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell 141:583–594PubMedCrossRefGoogle Scholar
  38. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (2008) Identification of cells initiating human melanomas. Nature 451:345–349PubMedCrossRefGoogle Scholar
  39. Schatton T, Schütte U, Frank NY, Zhan Q, Hoerning A, Robles SC, Zhou J, Hodi FS, Spagnoli GC, Murphy GF, Frank MH (2010) Modulation of T-cell activation by malignant melanoma initiating cells. Cancer Res 70:697–708PubMedCrossRefGoogle Scholar
  40. Short JJ, Curiel DT (2009) Oncolytic adenoviruses targeted to cancer stem cells. Mol Cancer Ther 8:2096–2102PubMedCrossRefGoogle Scholar
  41. Sikandar SS, Pate KT, Anderson S, Dizon D, Edwards RA, Waterman ML, Lipkin SM (2010) NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer. Cancer Res 70:1469–1478PubMedCrossRefGoogle Scholar
  42. Takahashi H, Ishii H, Nishida N, Takemasa I, Mizushima T, Ikeda M, Yokobori T, Mimori K, Yamamoto H, Sekimoto M, Doki Y, Mori M (2011) Significance of Lgr5(+ve) cancer stem cells in the colon and rectum. Ann Surg Oncol 18:1166–1174PubMedCrossRefGoogle Scholar
  43. Takebe N, Harris PJ, Warren RQ, Ivy SP (2011) Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol 8:97–106PubMedCrossRefGoogle Scholar
  44. Tanaka H, Nakamura M, Kameda C, Kubo M, Sato N, Kuroki S, Tanaka M, Katano M (2009) The Hedgehog signaling pathway plays an essential role in maintaining the CD44+CD24−/low subpopulation and the side population of breast cancer cells. Anticancer Res 29:2147–2157PubMedGoogle Scholar
  45. Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1:389–402PubMedCrossRefGoogle Scholar
  46. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong, C, Huang Y, Hu X, Su F, Lieberman J, Song E (2007) Let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131:1109–1123PubMedCrossRefGoogle Scholar
  47. Yu F, Li J, Chen H, Fu J, Ray S, Huang S, Zheng H, Ai W (2011) Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion. Oncogene. [Epub ahead of print]. doi:10.1038/onc.2010.591Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Juan Antonio Marchal
    • 1
  • María Angel García
    • 2
    • 3
  • Houria Boulaiz
    • 3
  • Macarena Perán
    • 3
  • Pablo Álvarez
    • 1
  • José Carlos Prados
    • 1
  • Consolación Melguizo
    • 1
  • Antonia Aránega
    • 1
  1. 1.Department Anatomía y Embriología, Facultad de MedicinaInstitute of Biopathology and Regenerative Medicine (IBIMER), University of GranadaGranadaSpain
  2. 2.Unidad de Investigación, Hospital Universitario Virgen de las NievesGranadaSpain
  3. 3.Institute of Biopathology and Regenerative Medicine (IBIMER), University of GranadaGranadaSpain

Personalised recommendations