Journal of Breast Cancer

Korean Breast Cancer Society (한국유방암학회)
권호 표지
DOI QR코드

DOI QR Code

Aberrant Expression of Cancer Stem Cells Marker Prominin-1 in Low-Grade Tubulobular Breast Carcinoma: A Correlative Study between qRT-PCR, Flow-Cytometric and Immunohistochemistry Analysis

  • Bonito, Maurizio Di (Pathology Unit, National Cancer Institute, Pascale Hospital) ;
  • Collina, Francesca (Pathology Unit, National Cancer Institute, Pascale Hospital) ;
  • Cantile, Monica (Pathology Unit, National Cancer Institute, Pascale Hospital) ;
  • Camerlingo, Rosalba (Department of Experimental Oncology, National Cancer Institute, Pascale Hospital) ;
  • Cerrone, Margherita (Pathology Unit, National Cancer Institute, Pascale Hospital) ;
  • Marra, Laura (Pathology Unit, National Cancer Institute, Pascale Hospital) ;
  • Liguori, Giuseppina (Pathology Unit, National Cancer Institute, Pascale Hospital) ;
  • Pirozzi, Giuseppe (Department of Experimental Oncology, National Cancer Institute, Pascale Hospital) ;
  • Botti, Gerardo (Pathology Unit, National Cancer Institute, Pascale Hospital)
  • Published : 2012.03.30
⟨ Previous Next ⟩

Abstract

Purpose: Prominin1/CD133 has become the ideal marker for cancer stem cells (CSCs) detection in human tumors. In this study we examined the expression of this marker in several breast cancer specimens to associate CSCs percentage with risk factor for this neoplasia. Methods: We examined specimens from 12 patients using CD133 and CD44 antibodies for CSCs immunohistochemistry detection and for flow cytometry analysis. For each patient, we also performed the immunohistochemical staining to evaluate the expression of estrogen receptor, progesterone receptor, c-erbB-2, Ki67, and E-cadherin markers. A Taqman probe for CD133 was used for mRNA quantification by realtime polymerase chain reaction. Results: Prominin-1 expression was heterogeneous in different carcinomas but was strikingly hyperexpressed in a tubulolobular variant of breast cancer. The results were confirmed by all three methods. Conclusion: Our data, although produced on a limited number of samples, showed an particularly high expression of stem cell marker CD133 in a breast cancer variant, generally with a good prognosis. Since CSCs detection by CD133 has been described as an important prognostic factor for several human cancers, we suggest the importance of detecting stem cell compartiments in all histotypes of breast carcinomas.

Keywords

References

  1. Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med 2006;355:1253-61. https://doi.org/10.1056/NEJMra061808
  2. Ailles LE, Weissman IL. Cancer stem cells in solid tumors. Curr Opin Biotechnol 2007;18:460-6. https://doi.org/10.1016/j.copbio.2007.10.007
  3. Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene 2004;23:7274-82. https://doi.org/10.1038/sj.onc.1207947
  4. Maitland NJ, Collins AT. Cancer stem cells: a therapeutic target? Curr Opin Mol Ther 2010;12:662-73.
  5. Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci U S A 2009;106:13820-5. https://doi.org/10.1073/pnas.0905718106
  6. Kim HJ, Kim JB, Lee KM, Shin I, Han W, Ko E, et al. Isolation of CD24(high) and CD24(low/-) cells from MCF-7: CD24 expression is positively related with proliferation, adhesion and invasion in MCF-7. Cancer Lett 2007;258:98-108. https://doi.org/10.1016/j.canlet.2007.08.025
  7. Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, et al. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 2006;8:R59. https://doi.org/10.1186/bcr1610
  8. Honeth G, Bendahl PO, Ringner M, Saal LH, Gruvberger-Saal SK, Lovgren K, et al. The CD44+/CD24- phenotype is enriched in basallike breast tumors. Breast Cancer Res 2008;10:R53. https://doi.org/10.1186/bcr2108
  9. Rappa G, Lorico A. Phenotypic characterization of mammosphereforming cells from the human MA-11 breast carcinoma cell line. Exp Cell Res 2010;316:1576-86. https://doi.org/10.1016/j.yexcr.2010.01.012
  10. Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 1997;90:5013-21.
  11. Fargeas CA, Corbeil D, Huttner WB. AC133 antigen, CD133, prominin- 1, prominin-2, etc.: prominin family gene products in need of a rational nomenclature. Stem Cells 2003;21:506-8. https://doi.org/10.1634/stemcells.21-4-506
  12. Wu Y, Wu PY. CD133 as a marker for cancer stem cells: progresses and concerns. Stem Cells Dev 2009;18:1127-34. https://doi.org/10.1089/scd.2008.0338
  13. Liu Q, Li JG, Zheng XY, Jin F, Dong HT. Expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas. Chin Med J (Engl) 2009;122:2763-9.
  14. Zhao P, Lu Y, Jiang X, Li X. Clinicopathological significance and prognostic value of CD133 expression in triple-negative breast carcinoma. Cancer Sci 2011;102:1107-11. https://doi.org/10.1111/j.1349-7006.2011.01894.x
  15. Lorico A, Rappa G. Phenotypic heterogeneity of breast cancer stem cells. J Oncol 2011;2011:135039.
  16. Al-Mulla F, Abdulrahman M, Varadharaj G, Akhter N, Anim JT. BRCA1 gene expression in breast cancer: a correlative study between real-time RT-PCR and immunohistochemistry. J Histochem Cytochem 2005;53: 621-9. https://doi.org/10.1369/jhc.4A6544.2005
  17. Chumas J. Tubulolobular carcinoma of the breast. Am J Surg Pathol 1998;22:903-4.
  18. Mimeault M, Batra SK. New promising drug targets in cancer- and metastasis- initiating cells. Drug Discov Today 2010;15:354-64. https://doi.org/10.1016/j.drudis.2010.03.009
  19. Takebe N, Harris PJ, Warren RQ, Ivy SP. Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol 2011;8:97-106. https://doi.org/10.1038/nrclinonc.2010.196
  20. Ferrandina G, Petrillo M, Bonanno G, Scambia G. Targeting CD133 antigen in cancer. Expert Opin Ther Targets 2009;13:823-37. https://doi.org/10.1517/14728220903005616
  21. Rappa G, Fodstad O, Lorico A. The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma. Stem Cells 2008;26:3008-17. https://doi.org/10.1634/stemcells.2008-0601
  22. Smith LM, Nesterova A, Ryan MC, Duniho S, Jonas M, Anderson M, et al. CD133/prominin-1 is a potential therapeutic target for antibodydrug conjugates in hepatocellular and gastric cancers. Br J Cancer 2008; 99:100-9. https://doi.org/10.1038/sj.bjc.6604437

Cited by

  1. Clinicopathological significance of cancer stem cells marked by CD133 and KAI1/CD82 expression in laryngeal squamous cell carcinoma vol.12, pp.None, 2012, https://doi.org/10.1186/1477-7819-12-118
  2. Clinicopathological Significance of CD133 and ALDH1 Cancer Stem Cell Marker Expression in Invasive Ductal Breast Carcinoma vol.16, pp.17, 2012, https://doi.org/10.7314/apjcp.2015.16.17.7491