Skip to main content

Advertisement

Log in

CD133+ single cell-derived progenies of colorectal cancer cell line SW480 with different invasive and metastatic potential

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Single cell progenies (SCPs) inherit biological properties from their isogenetic mother cells. If a single cancer cell can give rise to progenies, which can be passaged sustainably in vitro and produce tumor in xenotransplantation, the cell should be cancer initiating cell. CD133 (Prominin-1, Prom1) is the marker of human colorectal cancer (CRC) stem cells and probably a marker of metastatic cancer stem cells (CSCs). Thirty-three SCPs of CRC cell line SW480 were isolated by limited dilution methods, thirty of which are CD133 positive and three negative. All of the CD133+ SCPs are tumorigenic, and the subcutaneous tumors expanded rapidly, while only 1 of 3 CD133 SCPs developed a minimal tumor in nude mice. Orthotopic transplantation experiments showed that CD133+ SCPs possessed heterogeneity in intestinal wall invasion, lymph node and liver metastases. CD133+ SCPs varied in cell growth, invasive ability, epithelial-mesenchymal-transition and expression of CSCs markers (CD133, CD44, and CXCR4) associated with metastatic potential. CD133 SCPs did not produce secondary transplanted tumor, intestinal invasion and metastasis. The results indicated CD133+ subpopulation of SW480 SCPs bear heterogeneous invasive and metastatic ability, and CRC-CSCs might be a heterogeous subpopulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

SCPs:

Single cell progenies

CRC:

Colorectal carcinoma

CSCs:

Cancer stem cells

EMT:

Epithelial-mesenchymal-transition

FCS:

Fetal calf serum

PBS:

Phosphate-buffered saline

FITC:

Fluoresceine isothiocyanate

DAPI:

4,6-Diamino-2-phenyl indole

TRITC:

Tetramethyl rhodamine isothiocyanate

References

  1. Nelson H, Petrelli N, Carlin A et al (2001) Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 93(8):583–596

    Article  CAS  PubMed  Google Scholar 

  2. O’Connell JB, Maggard MA, Ko CY (2004) Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst 96(19):1420–1425

    Article  PubMed  Google Scholar 

  3. Miller SJ, Lavker RM, Sun TT (2005) Interpreting epithelial cancer biology in the context of stem cells: tumor properties and therapeutic implications. Biochim Biophys Acta 1756(1):25–52

    CAS  PubMed  Google Scholar 

  4. Al-Hajj M, Becker MW, Wicha M et al (2004) Therapeutic implications of cancer stem cells. Curr Opin Genet Dev 14(1):43–47

    Article  CAS  PubMed  Google Scholar 

  5. Brabletz T, Jung A, Spaderna S et al (2005) Opinion: migrating cancer stem cells—an integrated concept of malignant tumour progression. Nat Rev Cancer 5(9):744–749

    Article  CAS  PubMed  Google Scholar 

  6. O’Brien CA, Pollett A, Gallinger S et al (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110

    Article  PubMed  Google Scholar 

  7. Ricci-Vitiani L, Lombardi DG, Pilozzi E et al (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115

    Article  CAS  PubMed  Google Scholar 

  8. Dalerba P, Dylla SJ, Park IK et al (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104(24):10158–10163

    Article  CAS  PubMed  Google Scholar 

  9. Li CY, Li BX, Liang Y et al (2009) Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB. J Transl Med 7:56

    Article  CAS  PubMed  Google Scholar 

  10. Choi D, Lee HW, Hur KY et al (2009) Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma. World J Gastroenterol 15(18):2258–2264

    Article  CAS  PubMed  Google Scholar 

  11. Horst D, Scheel SK, Liebmann S et al (2009) The cancer stem cell marker CD133 has high prognostic impact but unknown functional relevance for the metastasis of human colon cancer. J Pathol 219(4):427–434

    Article  CAS  PubMed  Google Scholar 

  12. Wang Q, Chen ZG, Du CZ et al (2009) Cancer stem cell marker CD133+ tumour cells and clinical outcome in rectal cancer. Histopathology 55(3):284–293

    Article  PubMed  Google Scholar 

  13. Horst D, Kriegl L, Engel J et al (2008) CD133 expression is an independent prognostic marker for low survival in colorectal cancer. Br J Cancer 99(8):1285–1289

    Article  CAS  PubMed  Google Scholar 

  14. Horst D, Kriegl L, Engel J et al (2009) Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer. Cancer Invest 27(8):844–850

    Article  PubMed  Google Scholar 

  15. Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9(4):265–273

    Article  CAS  PubMed  Google Scholar 

  16. Mani SA, Guo W, Liao MJ et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715

    Article  CAS  PubMed  Google Scholar 

  17. Hugo H, Ackland ML, Blick T et al (2007) Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol 213(2):374–383

    Article  CAS  PubMed  Google Scholar 

  18. Joyce T, Cantarella D, Isella C et al (2009) A molecular signature for epithelial to mesenchymal transition in a human colon cancer cell system is revealed by large-scale microarray analysis. Clin Exp Metastasis 26(6):569–587

    Article  CAS  PubMed  Google Scholar 

  19. Singh SK, Clarke ID, Terasaki M et al (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828

    CAS  PubMed  Google Scholar 

  20. Singh SK, Hawkins C, Clarke ID et al (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401

    Article  CAS  PubMed  Google Scholar 

  21. Collins AT, Berry PA, Hyde C et al (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65(23):10946–10951

    Article  CAS  PubMed  Google Scholar 

  22. Vander Griend DJ, Karthaus WL, Dalrymple S et al (2008) The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells. Cancer Res 68(23):9703–9711

    Article  CAS  PubMed  Google Scholar 

  23. Yin S, Li J, Hu C et al (2007) CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer 120(7):1444–1450

    Article  CAS  PubMed  Google Scholar 

  24. Hermann PC, Huber SL, Herrler T et al (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323

    Article  CAS  PubMed  Google Scholar 

  25. Eramo A, Lotti F, Sette G et al (2008) Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 15(3):504–514

    Article  CAS  PubMed  Google Scholar 

  26. Cox CV, Diamanti P, Evely RS et al (2009) Expression of CD133 on leukemia-initiating cells in childhood ALL. Blood 113(14):3287–3296

    Article  CAS  PubMed  Google Scholar 

  27. 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(12):3008–3017

    Article  CAS  PubMed  Google Scholar 

  28. Shmelkov SV, Butler JM, Hooper AT et al (2008) CD133 expression is not restricted to stem cells, and both CD133+ and CD133 metastatic colon cancer cells initiate tumors. J Clin Invest 118(6):2111–2120

    CAS  PubMed  Google Scholar 

  29. LaBarge MA, Bissell MJ (2008) Is CD133 a marker of metastatic colon cancer stem cells? J Clin Invest 118(6):2021–2024

    CAS  PubMed  Google Scholar 

  30. Liu L, Zhang Q, Zhang Y et al (2006) Lentivirus-mediated silencing of Tiam1 gene influences multiple functions of a human colorectal cancer cell line. Neoplasia 8(11):917–924

    Article  CAS  PubMed  Google Scholar 

  31. Quintana E, Shackleton M, Sabel MS et al (2008) Efficient tumour formation by single human melanoma cells. Nature 456(7222):593–598

    Article  CAS  PubMed  Google Scholar 

  32. Hao JM, Chen JZ, Sui HM et al (2010) A five-gene signature as a potential predictor of metastasis and survival in colorectal cancer. J Pathol 220(4):475–489

    CAS  PubMed  Google Scholar 

  33. Haraguchi N, Ohkuma M, Sakashita H et al (2008) CD133+ CD44+ population efficiently enriches colon cancer initiating cells. Ann Surg Oncol 15(10):2927–2933

    Article  PubMed  Google Scholar 

  34. Reya T, Morrison SJ, Clarke MF et al (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111

    Article  CAS  PubMed  Google Scholar 

  35. Snippert HJ, van Es JH, van den Born M, et al (2009) Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine. Gastroenterology 136(7):2187–2194 e1

    Google Scholar 

  36. Yoshikawa S, Zen Y, Fujii T et al (2009) Characterization of CD133+ parenchymal cells in the liver: histology and culture. World J Gastroenterol 15(39):4896–4906

    Article  CAS  PubMed  Google Scholar 

  37. Beier D, Hau P, Proescholdt M et al (2007) CD133(+) and CD133(−) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 67(9):4010–4015

    Article  CAS  PubMed  Google Scholar 

  38. Lottaz C, Beier D, Meyer K et al (2010) Transcriptional profiles of CD133+ and CD133 glioblastoma-derived cancer stem cell lines suggest different cells of origin. Cancer Res 70(5):2030–2040

    Article  CAS  PubMed  Google Scholar 

  39. Meng X, Li M, Wang X et al (2009) Both CD133+ and CD133 subpopulations of A549 and H446 cells contain cancer-initiating cells. Cancer Sci 100(6):1040–1046

    Article  CAS  PubMed  Google Scholar 

  40. Pece S, Tosoni D, Confalonieri S et al (2010) Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 140(1):62–73

    Article  CAS  PubMed  Google Scholar 

  41. Barker N, van Es JH, Kuipers J et al (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449(7165):1003–1007

    Article  CAS  PubMed  Google Scholar 

  42. Sato T, Vries RG, Snippert HJ et al (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459(7244):262–265

    Article  CAS  PubMed  Google Scholar 

  43. Zhu L, Gibson P, Currle DS et al (2009) Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 457(7229):603–607

    Article  CAS  PubMed  Google Scholar 

  44. Morimoto-Tomita M, Ohashi Y, Matsubara A et al (2005) Mouse colon carcinoma cells established for high incidence of experimental hepatic metastasis exhibit accelerated and anchorage-independent growth. Clin Exp Metastasis 22(6):513–521

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Basic Research Program of China (973 Program, No 2010CB529403). This work was funded by the National Nature Science Foundation of China (Grants 30801380, 30770977 and 30670967) and Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, No. IRT0731). This work was also supported by Municipal Programs of Guangzhou for Science and Technology Development (No. 2007Z3-E4011).

Conflict of interest statement

None.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yongjian Deng or Yanqing Ding.

Additional information

Guangqiu Li and Chao Liu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, G., Liu, C., Yuan, J. et al. CD133+ single cell-derived progenies of colorectal cancer cell line SW480 with different invasive and metastatic potential. Clin Exp Metastasis 27, 517–527 (2010). https://doi.org/10.1007/s10585-010-9341-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-010-9341-0

Keywords

Navigation