Antisense insulin-like growth factor I transferred into a rat hepatoma cell line inhibits tumorigenesis by modulating major histocompatibility complex I cell surface expression

Cancer Gene Ther. Sep-Oct 1997;4(5):276-85.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B7-1 Antigen / biosynthesis
  • Blotting, Northern
  • Cell Division
  • Flow Cytometry
  • Genetic Therapy*
  • Glioma / genetics
  • Glioma / immunology
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / immunology
  • Histocytochemistry
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / biosynthesis
  • Insulin-Like Growth Factor I / genetics*
  • Liver Neoplasms, Experimental / immunology
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / therapy*
  • RNA, Antisense / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Transfection
  • Tumor Cells, Cultured

Substances

  • B7-1 Antigen
  • Histocompatibility Antigens Class I
  • RNA, Antisense
  • RNA, Messenger
  • Insulin-Like Growth Factor I