Antisense insulin-like growth factor I transferred into a rat hepatoma cell line inhibits tumorigenesis by modulating major histocompatibility complex I cell surface expression.
We have established a hepatocarcinoma cell line (LFCI2 A) that produces voluminous tumors when injected subcutaneously into syngeneic Commentry rats. These neoplastic cells express both insulin-like growth factors (IGF) I and II. When transfected with an episomal cassette-expressing IGF-I antisense RNA, the modified LFCI2 A cell lines become poorly tumorigenic and, when injected subcutaneously, are associated with inhibition of the growth of the parental tumoral cells and/or induction of regression of established tumors. By contrast, cell lines isolated after transfection with the IGF-II antisense-expressing vector were as tumorigenic as the parental cell lines. The results are discussed in terms of protective immunity induced by the tumoral cells transfected by the IGF-I antisense vector. In the transfected hepatocarcinoma cells that do not produce IGF-I, the expression of major histocompatibility complex class I antigen was increased at least 4-fold compared with parental cells. The introduction of these cells in vivo induced a tumor-specific immunity that was associated with CD8 T cells.
Lafarge-Frayssinet
C
C
Laboratory of Molecular Genetics, UPR 42 CNRS, Institut de Recherches sur le Cancer IFC 1, Villejuif, France.
Duc
H T
HT
Frayssinet
C
C
Sarasin
A
A
Anthony
D
D
Guo
Y
Y
Trojan
J
J
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis; D015152:Blotting, Northern; D002455:Cell Division; D005434:Flow Cytometry; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D016372:RNA, Antisense; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I