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Subcutaneous passage increases cell aggressiveness in a xenograft model of diffuse large B cell lymphoma

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Abstract

Xenograft models of human diffuse large B cell lymphoma (DLBCL) are widely used to test new drugs against this neoplasia. Most of them, however, are subcutaneous xenografts that do not show a disseminated disease as it is found in the human neoplasia. In this paper, we aimed to develop a disseminated xenograft model of DLBCL by performing a subcutaneous passage of DLBCL cells before their intravenous injection in mice. WSU-DLCL-2 (WSU) cells were injected into both flanks of NOD/SCID mice. The subcutaneous tumours were disaggregated and a cell suspension (WSU-SC) was obtained. Two groups of 10 NOD/SCID mice were intravenously injected with WSU-SC or WSU cells. All mice injected with WSU-SC cells developed lymphoma in 32–47 days and showed lymph node and bone marrow infiltration. WSU-SC cells showed a significantly higher engraftment rate and faster dissemination than WSU cells after intravenous injection in mice. When molecularly compared, WSU-SC cells showed higher expression levels of FAK, p130Cas and phosphorylated AKT than WSU cells. The subcutaneous passage enhanced the engraftment and the metastatic capacity of WSU cells, allowing the generation of a rapid and disseminated DLBCL xenograft model. The aggressive behaviour of WSU-SC cells was associated with increased p130Cas and FAK expression and AKT activation.

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Abbreviations

DLBCL:

Diffuse large B cell lymphoma

CHOP:

Cyclophosphamide, doxorubicin, vincristine and prednisone

GEM:

Genetically engineered mice

WSU-SC:

WSU cell line after subcutaneous passage

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Acknowledgments

The authors would like to thank Cristo Cámara, Mariona Madero and Mónica Gómez for their technical support. We would also like to thank Carolyn Newey for English text revision and editing. This work was supported by Instituto de Salud Carlos III [FIS PS09/00965 to R. M., FIS PI080672 to J. S., FI08/00007 to R. B., Sara Borrell CD09/00014 to R. D.]; MiCINN [PIB2010BZ-00563 to R. M.]; CIBER-BBN [CBV6/01/1031 to R. M.]; and Fundació d’Investigació Sant Pau.

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Authors and Affiliations

  1. Grup d’Oncogènesi i Antitumorals (GOA), Institut d’Investigacions Biomèdiques Sant Pau, Pavelló 19 1r pis, Av. Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain

    Rosa Bosch, María José Moreno, Rebeca Dieguez-Gonzalez, María Virtudes Céspedes, Miguel Ángel Pavón, Isolda Casanova & Ramon Mangues

  2. Networking Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain

    Rosa Bosch, María Virtudes Céspedes, Miguel Ángel Pavón, Isolda Casanova & Ramon Mangues

  3. Department of Pathology, Clínica Girona, Girona, Spain

    Alberto Gallardo

  4. Department of Hematology and Laboratory, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Josep Nomdedeu

  5. Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Iñigo Espinosa

  6. Department of Pharmacy, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Maria Antònia Mangues

  7. Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Jorge Sierra

Authors
  1. Rosa Bosch
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  2. María José Moreno
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  3. Rebeca Dieguez-Gonzalez
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  4. María Virtudes Céspedes
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  5. Alberto Gallardo
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  6. Josep Nomdedeu
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  7. Miguel Ángel Pavón
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  8. Iñigo Espinosa
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  9. Maria Antònia Mangues
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  10. Jorge Sierra
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  11. Isolda Casanova
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  12. Ramon Mangues
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Corresponding authors

Correspondence to Isolda Casanova or Ramon Mangues.

Additional information

Isolda Casanova and Ramon Mangues contributed equally to this manuscript.

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Bosch, R., Moreno, M.J., Dieguez-Gonzalez, R. et al. Subcutaneous passage increases cell aggressiveness in a xenograft model of diffuse large B cell lymphoma. Clin Exp Metastasis 29, 339–347 (2012). https://doi.org/10.1007/s10585-012-9454-8

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  • DOI: https://doi.org/10.1007/s10585-012-9454-8

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