Impaired tumorigenicity and decreased liver metastasis of murine neuroblastoma cells engineered to secrete interleukin-2 or granulocyte macrophage colony-stimulating factor.
We have examined the antitumor effect of murine neuroblastoma cells (C1300) engineered to produce cytokines. Retrovirally transduced cells with human interleukin-2 (IL-2) or murine GM-CSF gene, but not murine IL-4 gene, abolished their tumorigenicity in syngeneic mice, although their in vitro growth rate and expression of class I antigens of the major histocompatibility complex were unchanged. Inoculation of wild-type cells into the mice, which had rejected IL-2 or GM-CSF producers, did not develop tumors, indicating that protective immunity was induced. In an experimental hematogenous metastasis model, we found that the numbers of metastatic foci in the liver caused by intravenous administration of IL-2 or GM-CSF producers were significantly reduced compared with those by the injection of wild-type or vector virus-transduced cells. No significant differences in their adhesiveness to extracellular matrices and ability to differentiate were observed among parent and transduced cells. Thus, these results indicate that IL-2 or GM-CSF secretion, in the vicinity of neuroblastoma cells, produced antitumor effect and reduced metastatic ability.
Yoshida
H
H
Department of Pediatric Surgery, School of Medicine, Chiba University, Japan.
Enomoto
H
H
Tagawa
M
M
Takenaga
K
K
Tasaki
K
K
Nakagawara
A
A
Ohnuma
N
N
Takahashi
H
H
Sakiyama
S
S
D000818:Animals; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000473:pathology; D015316:Genetic Therapy; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000556:secondary*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic
D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor