In Vivo Rat Model to Study Horizontal Tumor Progression

  • Catalina Trejo-Becerril
  • Enrique Pérez-Cárdenas
  • Alfonso Dueñas-GonzálezEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1165)


Most cancer deaths are due to metastases. Metastasis is an extraordinarily complex process by which cancer cells complete a sequential series of steps before they transform into a clinically detectable lesion. These steps typically include separation from the primary tumor, invasion through surrounding tissues and basement membranes, entry and survival in the circulation, lymphatic or peritoneal space, and arrest in a distant target organ and the formation of secondary tumors in distant organs.

While proposed or accepted models and mechanisms of metastatic progression, have been demonstrated in experimental systems, none of them sufficiently explain all of the complexities associated with this process. These models can broadly be classified into two types, those occurring by vertical gene transfer (Darwinian) and those involving horizontal or lateral DNA transfer. Here, we describe an experimental system to study the metastatic process involving the horizontal transfer of circulating DNA.

Key words

Horizontal tumor progression Circulating DNA Horizontal transfer 


  1. 1.
    Liotta LA, Kohn E (2004) Anoikis; cancer and the homeless cell. Nature 430:973–974PubMedCrossRefGoogle Scholar
  2. 2.
    Geiger TR, Peeper DS (2009) Metastasis mechanisms. Biochim Biophys Acta 1796:293–308PubMedGoogle Scholar
  3. 3.
    Hunter KW, Crawford NP, Alsarraj J (2008) Mechanisms of metastasis. Breast Cancer Res 10(Suppl 1):S2PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194:23–28PubMedCrossRefGoogle Scholar
  5. 5.
    Porter RD (1988) Modes of gene transfer in bacteria. In: Kucherlapati R, Smith GR (eds) Genetic recombination. ASM, Washington, DC, p 1Google Scholar
  6. 6.
    Mishra NC (1985) Gene transfer in fungi. Adv Genet 23:73PubMedCrossRefGoogle Scholar
  7. 7.
    Klein BY (1981) A suggested mechanism for changing tumor cell phenotype: transfection of host cells with DNA sequences of dead tumor cells. Med Hypotheses 7:645–650PubMedCrossRefGoogle Scholar
  8. 8.
    Holmgrem L, Szeles A, Rajnavolgyi E et al (1999) Horizontal transfer of DNA by the uptake of apoptotic bodies. Blood 93:3956–3963Google Scholar
  9. 9.
    Goldenberg DM, Gold DV, Loo M et al (2013) Horizontal transmission of malignancy: in-vivo fusion of human lymphomas with hamster stroma produces tumors retaining human genes and lymphoid pathology. Plos One 8:e55324PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Bendich A, Wilczok T, Borenfreund E (1965) Circulating DNA as a possible factor in oncogenesis. Science 148:374–376PubMedCrossRefGoogle Scholar
  11. 11.
    García-Olmo D, García-Olmo DC, Ontañón J et al (1999) Tumor DNA circulating in the plasma might play a role in metastasis. The hypothesis of the genometastasis. Histol Histopathol 14:1159–1164PubMedGoogle Scholar
  12. 12.
    Trejo-Becerril C, Pérez-Cárdenas E, Treviño-Cuevas H et al (2003) Circulating nucleosomes and response to chemotherapy: an in vitro, in vivo and clinical study on cervical cancer patients. Int J Cancer 104:663–668PubMedCrossRefGoogle Scholar
  13. 13.
    Leon SA, Shapiro B, Sklaroff DM et al (1977) Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 37:646–650PubMedGoogle Scholar
  14. 14.
    Trejo-Becerril C, Oñate-Ocaña LF, Taja-Chayeb L et al (2005) Serum nucleosomes during neoadjuvant chemotherapy in patients with cervical cancer. Predictive and prognostic significance. BMC Cancer 5:65PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Vlassov VV, Laktionov PP, Rykova EY (2010) Circulating nucleic acids as a potential source for cancer biomarkers. Curr Mol Med 10:142–165PubMedCrossRefGoogle Scholar
  16. 16.
    Gahan PB (2012) Biology of circulating nucleic acids and possible roles in diagnosis and treatment in diabetes and cancer. Infect Disord Drug Targets 12:360–370PubMedCrossRefGoogle Scholar
  17. 17.
    Record M, Subra C, Silvente-Poirot S et al (2011) Exosomes as intercellular signalosomes and pharmacological effectors. Biochem Pharmacol 81:1171–1182PubMedCrossRefGoogle Scholar
  18. 18.
    Stroun M (1989) Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology 46:318–322PubMedCrossRefGoogle Scholar
  19. 19.
    García-Olmo DC, Domínguez C, García-Arranz M et al (2010) Cell-free nucleic acids circulating in the plasma of colorectal cancer patients induce the oncogenic transformation of susceptible cultured cells. Cancer Res 70:560–567PubMedCrossRefGoogle Scholar
  20. 20.
    Trejo-Becerril C, Pérez-Cárdenas E, Taja-Chayeb L et al (2012) Cancer progression mediated by horizontal gene transfer in an in vivo model. Plos One 7:e52754PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Perse M, Cerar A (2005) The dimethylhydrazine induced colorectal tumors in rat-experimental colorectal carcinogenesis. Radiol and Oncol 39:61–70Google Scholar
  22. 22.
    Patutina O, Mironova N, Ryabchikova E et al (2011) Inhibition of metastasis development by daily administration of ultralow doses of RNase A and DNase I. Biochimie 93:689–696PubMedCrossRefGoogle Scholar
  23. 23.
    Walker JA, Kilroy GE, Xing J et al (2003) Human DNA quantitation using Alu element-based polymerase chain reaction. Anal Biochem 315:122–128PubMedCrossRefGoogle Scholar
  24. 24.
    Soares MB, Schon E, Efstratiadis A (1985) Rat LINE1: the origin and evolution of a family of long interspersed middle repetitive DNA elements. J Mol Evol 22:117–133PubMedCrossRefGoogle Scholar
  25. 25.
    Madara JL, Harte P, Deasy J et al (1983) Evidence for an adenomacarcinoma sequence in dimethylhydrazine-induced neoplasms of rat intestinal epithelium. Am J Pathol 110:230–235PubMedCentralPubMedGoogle Scholar
  26. 26.
    Watanabe H, Uesaka T, Kido S et al (1999) Gastric tumor induction by 1,2-dimethyl hydrazine in Wistar rats with intestinal metaplasia caused by X-irradiation. Jpn J Cancer Res 90:1207–1211Google Scholar
  27. 27.
    Ravnik-Glavac M, Cerar A, Glavac D (2000) Animal model in the study of colorectal carcinogenesis. Eur J Physiol 440:R55–R57CrossRefGoogle Scholar
  28. 28.
    Wald M, Olejár T, Poucková P et al (1998) Proteinases reduce metastatic dissemination and increase survival time in C57B16 mice with the Lewis lung carcinoma. Life Sciences 63:L237–L243CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Catalina Trejo-Becerril
    • 1
  • Enrique Pérez-Cárdenas
    • 1
  • Alfonso Dueñas-González
    • 2
    • 3
    Email author
  1. 1.Division of Basic ResearchInstituto Nacional de CancerologíaMéxico CityMéxico
  2. 2.Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México UNAM/Instituto Nacional de CancerologíaMéxico CityMéxico
  3. 3.Primer Piso, Edificio de InvestigaciónMéxico CityMéxico

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