Skip to main content

Advertisement

SpringerLink
Log in

Characterization and comparison of telomere length, telomerase and reverse transcriptase activity and gene expression in human mesenchymal stem cells and cancer cells of various origins

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

We have characterized and compared the telomere length, telomerase, reverse transcriptase (RT) activity and expression of genes implicated in cancer and in pluripotency, in human mesenchymal stem cells (MSCs) derived from dental papilla tissue, umbilical cord matrix and adipose tissue and in cancer cells (MDA-MB-231, U-87 MG, and MCF-7). MRC-5 fetal fibroblasts and adult muscle cells were used as somatic cell controls. Telomere length was significantly (P < 0.05) higher in MSCs and somatic cells (7.2-9.3 kb) than in cancer cell lines (3.9-6 kb). However, the relative telomerase activity (RTA) in the cancer cell lines was significantly (P < 0.05) higher than that of MSCs and somatic cells. RTA tended to be slightly higher in MSCs but no significant differences were observed between some cancer cells and MSCs. However, RTA was not detected in somatic cells. Although differentially displayed, the expression of genes related to cancer (BCL-2, p53, NF-κB, TGF-β, VEGF) and transcription and pluripotency (OCT4, NANOG, STAT3, REX1) were commonly observed in MSCs and cancer cells. Thus, endogenous non-telomerase RTA might be a potential biological marker or regulator among MSCs and cancer cells. Further, by sharing the biological and molecular markers of self-renewal and proliferation with cancer cells, MSCs might play a contributory role as tissue resident stem cells in tumor development.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  • Akar U, Chaves-Reyez A, Barria M, Tari A, Sanguino A, Kondo Y, Kondo S, Arun B, Lopez-Berestein G, Ozpolat B (2008) Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells. Autophagy 4:669–679

    PubMed  CAS  Google Scholar 

  • Armesilla-Diaz A, Elvira G, Silva A (2009) p53 regulates the proliferation, differentiation and spontaneous transformation of mesenchymal stem cells. Exp Cell Res 315:3598–3610

    Article  PubMed  CAS  Google Scholar 

  • Artandi SE, DePinho RA (2010) Telomeres and telomerase in cancer. Carcinogenesis 31:9–18

    Article  PubMed  CAS  Google Scholar 

  • Beraldi R, Pittoggi C, Sciamanna I, Mattei E, Spadafora C (2006) Expression of LINE-1 retroposons is essential for murine preimplantation development. Mol Reprod Dev 73:279–287

    Article  PubMed  CAS  Google Scholar 

  • Chang CC, Shieh GS, Wu P, Lin CC, Shiau AL, Wu CL (2008) Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells. Cancer Res 68:6281–6291

    Article  PubMed  CAS  Google Scholar 

  • Cheng PH, Snyder B, Fillos D, Ibegbu CC, Huang AHC, Chan AWS (2008) Postnatal stem/progenitor cells derived from the dental pulp of adult chimpanzee. BMC Cell Biol 9:20

    Article  PubMed  Google Scholar 

  • Dien J, Amin HM, Chiu N, Wong W, Frantz C, Chiu B, Mackey JR, Lai R (2006) Signal transducers and activators of transcription-3 up-regulates tissue inhibitor of metalloproteinase-1 expression and decreases invasiveness of breast cancer. Am J Pathol 169:633–642

    Article  PubMed  CAS  Google Scholar 

  • Ezeh UI, Turek PJ, Reijo Pera RA, Clark AT (2005) Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer 104:2255–2265

    Article  PubMed  CAS  Google Scholar 

  • Hiyama E, Hiyama K (2007) Telomere and telomerase in stem cells. Br J Cancer 96:1020–1024

    Article  PubMed  CAS  Google Scholar 

  • Izadpanah R, Trygg C, Patel B, Kriedt C, Dufour J, Gimble JM, Bunnell BA (2006) Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 99:1285–1297

    Article  PubMed  CAS  Google Scholar 

  • Järås M, Edqvist A, Rebetz J, Salford LG, Widegren B, Fan X (2006) Human short-term repopulating cells have enhanced telomerase reverse transcriptase expression. Blood 108:1084–1091

    Article  PubMed  Google Scholar 

  • Jeon BG, Coppola G, Perrault SD, Rho GJ, Betts DH, King WA (2008) S-adenosyl homocysteine treatment of adult female fibroblasts alters X-chromosome inactivation and improves in vitro embryo development after somatic cell nuclear transfer. Reproduction 135:815–828

    Article  PubMed  CAS  Google Scholar 

  • Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, Liu C, Calhoun-Davis T, Zaehres H, Daley GQ, Tang DG (2009) Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells 27:993–1005

    Article  PubMed  CAS  Google Scholar 

  • Kaus A, Widera D, Kassmer S, Peter J, Zaenker K, Kaltschmidt C, Kaltschmidt B (2010) Neural stem cells adopt tumorigenic properties by constitutively activated NF-κB and subsequent VEGF up-regulation. Stem Cells Dev 19:999–1015

    Article  PubMed  CAS  Google Scholar 

  • Kim J, Kang JW, Park JH, Choi Y, Choi KS, Park KD, Baek DH, Seong SK, Min HK, Kim HS (2008) Biological characterization of long-term cultured human mesenchymal stem cells. Arch Pharm Res 32:117–126

    Article  Google Scholar 

  • Lee MY, Lu A, Gudas LJ (2010) Transcriptional regulation of Rex1 (zfp42) in normal prostate epithelial cells and prostate cancer cells. J Cell Physiol 224:17–27

    PubMed  CAS  Google Scholar 

  • Li L, Tian H, Yue W, Zhu F, Li S, Li W (2011) Human mesenchymal stem cells play a dual role on tumor cell growth in vitro and in vivo. J Cell Physiol 226:1860-1867

    Article  PubMed  CAS  Google Scholar 

  • Madjd Z, Mehrjerdi AZ, Sharifi AM, Molanaei S, Shahzadi SZ, Asadi-Lari M (2004) CD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in breast tumors. Cancer Immun 9:4

    Google Scholar 

  • Mangiacasale R, Pittoggi C, Sciamanna I, Careddu A, Mattei E, Lorenzini R, Travaglini L, Landriscina M, Barone C, Nervi C, Lavia P, Spadafora C (2003) Exposure of normal and transformed cells to nevirapine, a reverse transcriptase inhibitor, reduces cell growth and promotes differentiation. Oncogene 22:2750–2761

    Article  PubMed  CAS  Google Scholar 

  • Mongan NP, Martin KM, Gudas LJ (2006) The putative human stem cell marker, Rex-1 (Zfp42): structural classification and expression in normal human epithelial and carcinoma cell cultures. Mol Carcinog 45:887–900

    Article  PubMed  CAS  Google Scholar 

  • Moses H, Barcellos-Hoff MH (2011) TGF-β biology in mammary development and breast cancer. Cold Spring Harb Perspect Biol 3:a003277

    Article  PubMed  Google Scholar 

  • Muehlberg FL, Song YH, Krohn A, Pinilla SP, Droll LH, Leng X, Seidensticker M, Ricke J, Altman AM, Devarajan E, Liu W, Arlinghaus LH, Alt EU (2009) Tissue-resident stem cells promote breast cancer growth and metastasis. Carcinogenesis 30:589–597

    Article  PubMed  CAS  Google Scholar 

  • Myers TL, Granero-Molto F, Longobardi L, Li T, Yan Y, Spagnoli A (2010) Mesenchymal stem cells at the intersection of cell and gene therapy. Expert Opin Biol Ther 10:1663–1679

    Article  PubMed  CAS  Google Scholar 

  • Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood 110:3499–3506

    Article  PubMed  CAS  Google Scholar 

  • Oricchio E, Sciamanna I, Beraldi R, Tolstonog GV, Schumann GG, Spadafora C (2007)Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression.Oncogene 26:4226-4233

    Article  PubMed  CAS  Google Scholar 

  • Parsch D, Fellenberg J, Brümmendorf TH, Eschlbeck AM, Richter W (2004) Telomere length and telomerase activity during expansion and differentiation of human mesenchymal stem cells and chondrocytes. J Mol Med 82:49–55

    Article  PubMed  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  • Prasad S, Ravindran J, Aggarwal BB (2010) NF-κB and cancer: how intimate is this relationship. Mol Cell Biochem 336:25–37

    Article  PubMed  CAS  Google Scholar 

  • Riekstina U, Cakstina I, Parfejevs V, Hoogduijn M, Jankovskis G, Muiznieks I, Muceniece R, Ancans J (2009) Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis. Stem Cell Rev 5:378–386

    Article  PubMed  CAS  Google Scholar 

  • Salem HK, Thiemermann C (2010) Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28:585–596

    PubMed  CAS  Google Scholar 

  • Sciamanna I, Landriscina M, Pittogi C, Quirino M, Mearelli C, Beraldi R, Mattei E, Serafino A, Cassano A, Sinibaldi-Vallebona P, Garaci E, Barone C, Spadofora C (2005) Inhibition of endogenous reverse transcriptase antagonizes human tumor growth. Oncogene 24:3923–3931

    Article  PubMed  CAS  Google Scholar 

  • Sciamanna I, Vitullo P, Curatolo A, Spadafora C (2009) Retrotransposons, reverse transcriptase and the genesis of new genetic information. Gene 448:180–186

    Article  PubMed  CAS  Google Scholar 

  • Serakinci N, Graakjaer J, Kolvraa S (2008) Telomere stability and telomerase in mesenchymal stem cells. Biochimie 90:33–40

    Article  PubMed  CAS  Google Scholar 

  • Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, Liu HJ, Gronthos S, Wang CY, Shi S, Wang S (2006) Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS ONE 1:e79

    Article  PubMed  Google Scholar 

  • Yamanaka S (2009) A fresh look at iPS cells. Cell 137:13–17

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Su P, Xu C, Chen C, Liang A, Du K, Peng Y, Huang D (2010) Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing PPARγ expression and enhancing Runx2 expression. J Pineal Res 49:364–372

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann S, Voss M, Kaiser S, Kapp U, Waller CF, Martens UM (2003) Lack of telomerase activity in human mesenchymal stem cells. Leukemia 17:1146–1149

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the BioGreen 21 (20070301034041 and 200908FHT010204005), Rural Development Administration, Republic of Korea.

Conflict of Interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. OBS/Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 900 Gazwa, Jinju, 660-701, Republic of Korea

    Byeong-Gyun Jeon, Basavarajappa Mohana Kumar, Eun-Ju Kang, Sun-A Ock, Sung-Lim Lee & Gyu-Jin Rho

  2. Department of Biology Education, College of Education, Gyeongsang National University, 900 Gazwa, Jinju, 660-701, Republic of Korea

    Dae-Oh Kwack

  3. Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju, 660-701, Republic of Korea

    June-Ho Byun & Bong-Wook Park

  4. Research Institute of Life Science, Gyeongsang National University, 900 Gazwa, Jinju, 660-701, Republic of Korea

    Gyu-Jin Rho

Authors
  1. Byeong-Gyun Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Basavarajappa Mohana Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eun-Ju Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sun-A Ock
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sung-Lim Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dae-Oh Kwack
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. June-Ho Byun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bong-Wook Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gyu-Jin Rho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gyu-Jin Rho.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jeon, BG., Kumar, B.M., Kang, EJ. et al. Characterization and comparison of telomere length, telomerase and reverse transcriptase activity and gene expression in human mesenchymal stem cells and cancer cells of various origins. Cell Tissue Res 345, 149–161 (2011). https://doi.org/10.1007/s00441-011-1191-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-011-1191-9

Keywords

Search

Navigation