Preferential proliferation of attenuated Salmonella typhimurium within neuroblastoma.
OBJECTIVE
Attenuated Salmonella typhimurium, a facultative intracellular parasite that colonizes the liver, has been shown to accumulate within extrahepatic malignancies. The authors sought to define a mechanism for attenuated Salmonella accumulation within cancer cells compared with hepatocytes.


METHODS
Invasion and intracellular proliferation of attenuated Salmonella was assessed through an in vitro assay performed on neuroblasoma, osteosarcoma, hepatoma, and colon adenocarcinoma cell lines and compared with freshly isolated mouse hepatocytes.


RESULTS
The efficiency of attenuated S typhimurium invasion into hepatocytes was greater than any malignant cell line (3.8 v 0.46; P <.04). However, the intracellular proliferation of the bacteria was most abundant within neuroblastoma, exceeding the proliferation within hepatocytes (14.3 v 6.2; P <.01).


CONCLUSIONS
Attenuated S typhimurium may prove to be an effective in vivo immunotherapy for the local delivery of therapeutic proteins to neuroblastoma.
Soto
Leland J
LJ
Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA.
Sorenson
Brent S
BS
Nelson
Brent W
BW
Solis
Scott J
SJ
Leonard
Arnold S
AS
Saltzman
Daniel A
DA
D000230:Adenocarcinoma / Q000473:pathology; D000262:Adenylyl Cyclases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D001223:Aspartate-Semialdehyde Dehydrogenase / Q000172:deficiency / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D001859:Bone Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor / Q000382:microbiology; D003110:Colonic Neoplasms / Q000473:pathology; D016503:Drug Delivery Systems; D017353:Gene Deletion; D005798:Genes, Bacterial; D022781:Hepatocytes / Q000382:microbiology; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology*; D009928:Organ Specificity; D012516:Osteosarcoma / Q000473:pathology; D051381:Rats; D011953:Receptors, Cyclic AMP / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D014169:Transformation, Bacterial; D014774:Virulence
D001426:Bacterial Proteins; D007376:Interleukin-2; D011953:Receptors, Cyclic AMP; D011994:Recombinant Proteins; D001223:Aspartate-Semialdehyde Dehydrogenase; D000262:Adenylyl Cyclases