title: Subcutaneous passage increases cell aggressiveness in a xenograft model of diffuse large B cell lymphoma.
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.
authors.affiliation: Grup d'Oncogènesi i Antitumorals, Institut d'Investigacions Biomèdiques Sant Pau, Pavelló 19 1r pis, Av. Sant Antoni Maria Claret, 167, 08025 Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bosch
authors.forename: María José
authors.initials: MJ
authors.lastname: Moreno
authors.forename: Rebeca
authors.initials: R
authors.lastname: Dieguez-Gonzalez
authors.forename: María Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.forename: Alberto
authors.initials: A
authors.lastname: Gallardo
authors.forename: Josep
authors.initials: J
authors.lastname: Nomdedeu
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Pavón
authors.forename: Iñigo
authors.initials: I
authors.lastname: Espinosa
authors.forename: Maria Antònia
authors.initials: MA
authors.lastname: Mangues
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.forename: Isolda
authors.initials: I
authors.lastname: Casanova
authors.forename: Ramon
authors.initials: R
authors.lastname: Mangues
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous / Q000473:pathology*