Suppression of tumorigenicity and metastasis in murine UV-2237 fibrosarcoma cells by infection with a retroviral vector harboring the interferon-beta gene

Cancer Immunol Immunother. 1998 May;46(3):137-46. doi: 10.1007/s002620050472.

Abstract

In this study, we endeavored to determine the effectiveness of interferon beta (IFNbeta) gene therapy against highly metastatic murine UV-2237m fibrosarcoma cells. UV-2237m cells were engineered to produce murine IFNbeta constitutively following infection by a retroviral vector harboring the murine IFNbeta gene. Parental (UV-2237m-P), control-vector-transduced (UV-2237m-Neo), and IFNbeta-transduced (UV-2237m-IFNbeta) cells were injected subcutaneously (s.c.) or intravenously (i.v.) into syngeneic mice. Parental and control-transduced cells produced rapidly growing tumors, whereas IFNbeta-transduced cells did not. The tumorigenicity of IFNbeta-sensitive or -resistant parental cells was significantly suppressed when they were injected s.c. together with IFNbeta-transduced cells. The IFNbeta-transduced cells did not inhibit growth of parental cells injected s.c. at a distant site. UV-2237m-IFNbeta cells produced s.c. tumors in nude, SCID/Beige, and natural killer(NK)-cell-compromised syngeneic mice. The IFNbeta-transduced cells were more sensitive to in vitro splenic cell-mediated lysis than were the parental or control-transduced cells. Pretreatment of C3H/HeN mice with the NK-cell-selective antiserum (anti-asialoGM1) partially abrogated the cytotoxic activity of the cells. Cytotoxic activity was not observed in mixed culture of UV-2237m-IFNbeta cells and splenic cells from SCID/Beige mice. Significant cytotoxicity against UV-2237m-IFNbeta cells was mediated by macrophages activated by either IFNgamma, lipopolysaccharide, or a combination of both. Our data led us to conclude that the constitutive expression of IFNbeta can suppress tumorigenicity and metastasis of UV-2237m cells, which is due, in part, to activation of host effector cells.

Publication types

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

MeSH terms

  • Animals
  • Carcinogenicity Tests
  • Cell Division / drug effects
  • Cell Transformation, Neoplastic / drug effects*
  • Cytotoxicity, Immunologic / immunology
  • Female
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / pathology*
  • Fibrosarcoma / secondary*
  • Genetic Engineering
  • Genetic Vectors / pharmacology*
  • Interferon-beta / biosynthesis
  • Interferon-beta / genetics*
  • Interferon-beta / pharmacology
  • Killer Cells, Natural / immunology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / secondary*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C3H
  • Mice, Knockout
  • Mice, Nude
  • Mice, SCID
  • Neoplasms, Experimental / pathology
  • Retroviridae / genetics*
  • Spleen / cytology
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects

Substances

  • Interferon-beta