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Vol. 75, No. 2, 2008
Issue release date: June 2008
Free Access
Pathobiology 2008;75:75–84
(DOI:10.1159/000123845)

Cancer Stem Cells in Breast: Current Opinion and Future Challenges

Charafe-Jauffret E.a-c · Monville F.a · Ginestier C.d · Dontu G.d · Birnbaum D.a · Wicha M.S.d
aDépartement d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, bDépartement de Biopathologie, Institut Paoli-Calmettes and UMR891 Inserm and cFaculté de Médecine, Université de la Méditerranée, Marseille, France; dDivision of Hematology/Oncology, Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan Medical Center, Ann Arbor, Mich., USA
email Corresponding Author

Abstract

There is increasing evidence for the cancer stem cell hypothesis, which holds that cancers are driven by a cellular subcomponent that has stem cell properties, that is, self-renewal, tumorigenicity and multilineage differentiation capacity. The cancer stem cell hypothesis modifies our conceptual approach of oncogenesis and shall have implications in breast cancer prevention, detection and treatment, especially in metastatic breast cancer for which no curative treatment exists. Given the specific stem cell features, novel therapeutic pathways can be targeted. Following this approach, new molecules are currently in development. Focusing on the cross-talk between stem cells and their microenvironment is also a promising way to explore how to better target cancer stem cells and be curative.


 goto top of outline Key Words

  • Breast cancer
  • Stem cell
  • Targeted therapy
  • Aldehyde dehydrogenase

 goto top of outline Abstract

There is increasing evidence for the cancer stem cell hypothesis, which holds that cancers are driven by a cellular subcomponent that has stem cell properties, that is, self-renewal, tumorigenicity and multilineage differentiation capacity. The cancer stem cell hypothesis modifies our conceptual approach of oncogenesis and shall have implications in breast cancer prevention, detection and treatment, especially in metastatic breast cancer for which no curative treatment exists. Given the specific stem cell features, novel therapeutic pathways can be targeted. Following this approach, new molecules are currently in development. Focusing on the cross-talk between stem cells and their microenvironment is also a promising way to explore how to better target cancer stem cells and be curative.

Copyright © 2008 S. Karger AG, Basel


 goto top of outline References
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  2. Anton Aparicio LM, Garcia CR, Cassinello EJ, Valladares AM, Reboredo LM, Diaz PS, Aparicio GG: Prostate cancer and Hedgehog signalling pathway. Clin Transl Oncol 2007;9:420–428.
  3. Ceder JA, Jansson L, Ehrnstrom RA, Ronnstrand L, Abrahamsson PA: The characterization of epithelial and stromal subsets of candidate stem/progenitor cells in the human adult prostate. Eur Urol 2008;53:524–532.
  4. Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C, De Maria R: Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 2008;15:504–514.
  5. Ferrandina G, Bonanno G, Pierelli L, Perillo A, Procoli A, Mariotti A, Corallo M, Martinelli E, Rutella S, Paglia A, Zannoni G, Mancuso S, Scambia G: Expression of CD133-1 and CD133-2 in ovarian cancer. Int J Gynecol Cancer 2007, E-pub ahead of print.
  6. Glinsky GV: Stem cell origin of death-from-cancer phenotypes of human prostate and breast cancers. Stem Cell Rev 2007;3:79–93.
  7. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM: Identification of pancreatic cancer stem cells. Cancer Res 2007;67:1030–1037.
  8. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007;104:973–978.
  9. Seo DC, Sung JM, Cho HJ, Yi H, Seo KH, Choi IS, Kim DK, Kim JS, Abd El-Aty AM, Shin HC: Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells. Mol Cancer 2007;6:75.
  10. Phillips TM, McBride WH, Pajonk F: The response of CD24–/low/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst 2006;98:1777–1785.
  11. Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G, Datar RH, Cote RJ: Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 2006;12:5615–5621.
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 goto top of outline Author Contacts

Emmanuelle Charafe-Jauffret
Département d’Oncologie Moléculaire, Institut Paoli-Calmettes
UMR891 Inserm, 232, Bd Sainte-Marguerite
FR–13273 Marseille Cedex 09 (France)
Tel. +33 491 225 457, Fax +33 491 223 573, E-Mail jauffrete@marseille.fnclcc.fr


 goto top of outline Article Information

Daniel Birnbaum and Max S. Wicha contributed equally.

Published online: June 10, 2008
Number of Print Pages : 10
Number of Figures : 1, Number of Tables : 0, Number of References : 75


 goto top of outline Publication Details

Pathobiology (Pathobiology - Exploring the basis of disease)

Vol. 75, No. 2, Year 2008 (Cover Date: June 2008)

Journal Editor: Borisch B. (Geneva), Yasui W. (Hiroshima)
ISSN: 1015–2008 (Print), eISSN: 1423–0291 (Online)

For additional information: http://www.karger.com/PAT


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

There is increasing evidence for the cancer stem cell hypothesis, which holds that cancers are driven by a cellular subcomponent that has stem cell properties, that is, self-renewal, tumorigenicity and multilineage differentiation capacity. The cancer stem cell hypothesis modifies our conceptual approach of oncogenesis and shall have implications in breast cancer prevention, detection and treatment, especially in metastatic breast cancer for which no curative treatment exists. Given the specific stem cell features, novel therapeutic pathways can be targeted. Following this approach, new molecules are currently in development. Focusing on the cross-talk between stem cells and their microenvironment is also a promising way to explore how to better target cancer stem cells and be curative.



 goto top of outline Author Contacts

Emmanuelle Charafe-Jauffret
Département d’Oncologie Moléculaire, Institut Paoli-Calmettes
UMR891 Inserm, 232, Bd Sainte-Marguerite
FR–13273 Marseille Cedex 09 (France)
Tel. +33 491 225 457, Fax +33 491 223 573, E-Mail jauffrete@marseille.fnclcc.fr


 goto top of outline Article Information

Daniel Birnbaum and Max S. Wicha contributed equally.

Published online: June 10, 2008
Number of Print Pages : 10
Number of Figures : 1, Number of Tables : 0, Number of References : 75


 goto top of outline Publication Details

Pathobiology (Pathobiology - Exploring the basis of disease)

Vol. 75, No. 2, Year 2008 (Cover Date: June 2008)

Journal Editor: Borisch B. (Geneva), Yasui W. (Hiroshima)
ISSN: 1015–2008 (Print), eISSN: 1423–0291 (Online)

For additional information: http://www.karger.com/PAT


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Bonnet D, Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997;3:730–737.
  2. Anton Aparicio LM, Garcia CR, Cassinello EJ, Valladares AM, Reboredo LM, Diaz PS, Aparicio GG: Prostate cancer and Hedgehog signalling pathway. Clin Transl Oncol 2007;9:420–428.
  3. Ceder JA, Jansson L, Ehrnstrom RA, Ronnstrand L, Abrahamsson PA: The characterization of epithelial and stromal subsets of candidate stem/progenitor cells in the human adult prostate. Eur Urol 2008;53:524–532.
  4. Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C, De Maria R: Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 2008;15:504–514.
  5. Ferrandina G, Bonanno G, Pierelli L, Perillo A, Procoli A, Mariotti A, Corallo M, Martinelli E, Rutella S, Paglia A, Zannoni G, Mancuso S, Scambia G: Expression of CD133-1 and CD133-2 in ovarian cancer. Int J Gynecol Cancer 2007, E-pub ahead of print.
  6. Glinsky GV: Stem cell origin of death-from-cancer phenotypes of human prostate and breast cancers. Stem Cell Rev 2007;3:79–93.
  7. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM: Identification of pancreatic cancer stem cells. Cancer Res 2007;67:1030–1037.
  8. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007;104:973–978.
  9. Seo DC, Sung JM, Cho HJ, Yi H, Seo KH, Choi IS, Kim DK, Kim JS, Abd El-Aty AM, Shin HC: Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells. Mol Cancer 2007;6:75.
  10. Phillips TM, McBride WH, Pajonk F: The response of CD24–/low/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst 2006;98:1777–1785.
  11. Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G, Datar RH, Cote RJ: Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 2006;12:5615–5621.
  12. Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R Jr, Badve S, Nakshatri H: CD44+/CD24– breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 2006;8:R59.
  13. Korkaya H, Iovino F, Wicha MS: PTEN and HER2 regulate self-renewal and invasion of human mammary stem cells. Proc Annu Meet Am Assoc Cancer Res 2007, abstr 1287.
  14. Jaiswal S, Traver D, Miyamoto T, Akashi K, Lagasse E, Weissman IL: Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias. Proc Natl Acad Sci USA 2003;100:10002–10007.
  15. Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG, Golub TR, Armstrong SA: Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 2006;442:818–822.
  16. 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: Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 2007;104:10158–10163.
  17. Wicha MS, Liu S, Dontu G: Cancer stem cells: an old idea – a paradigm shift. Cancer Res 2006;66:1883–1890.
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