title: Administration of a plasmid that expresses SDF-1α affects the oncogenic potential of mouse bcr-abl-transformed cells.
abstract: Stromal-derived factor 1α (SDF‑1α, also known as CXCL12) is a chemokine that exerts its effects through the G-protein coupled receptors, C-X-C chemokine receptor type 4 (CXCR4) and 7 (CXCR7). There is marked evidence that the SDF-1/CXCR4 axis is involved in the pathogenesis of leukemia and therapies that target this axis are under development. The present study aimed to increase the efficacy of a DNA-based bcr-abl vaccine by simultaneously immunizing mice with a plasmid carrying the whole SDF-1α gene. Bcr-abl‑transformed 12B1 cells were used to challenge the mice. These cells have the oncogenic potential to induce both leukemia following intravenous inoculation and lymphoma-type solid tumors after subcutaneous inoculation. Administering an SDF‑1 carrying plasmid together with the bcr-abl vaccine resulted in increased survival following a challenge with subcutaneously administered 12B1 cells, although the difference was not statistically significant. However, there was a difference when the animals that developed subcutaneous tumors were only taken into consideration. In doubly-treated mice, significantly more mice failed to develop solid tumors than mice that had only received the bcr-abl vaccine. By contrast, the occurrence of fatal leukemia was significantly higher in the mice that were treated with the SDF-1 plasmid, regardless of whether they were immunized with the bcr-abl-vaccine. No humoral or cellular immune responses against SDF‑1 were detected in the treated mice, which suggested that the changes in oncogenic potential of 12B1 cells were due to the activity of SDF-1 itself.
authors: Department of Experimental Virology, Institute of Hematology and Blood Transfusion, CZ-128 20 Prague 2, Czech Republic.
authors: Vincent
authors: V
authors: Lucansky
authors: Department of Experimental Virology, Institute of Hematology and Blood Transfusion, CZ-128 20 Prague 2, Czech Republic.
authors: Monika
authors: M
authors: Krmencikova-Fliegl
authors: Department of Experimental Virology, Institute of Hematology and Blood Transfusion, CZ-128 20 Prague 2, Czech Republic.
authors: Libor
authors: L
authors: Stanek
authors: Department of Experimental Virology, Institute of Hematology and Blood Transfusion, CZ-128 20 Prague 2, Czech Republic.
authors: Vladimir
authors: V
authors: Vonka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy / Q000662:veterinary; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015996:Survival Rate; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use
chemical_list: D054377:Chemokine CXCL12; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019718:Receptors, CXCR4; D019444:Vaccines, DNA; D016044:Fusion Proteins, bcr-abl