Modulation of graft-versus-tumor effects in a murine allogeneic bone marrow transplantation model by tumor-derived transforming growth factor-β1

Shivaani Kummar, Akihiro Ishii, Han Kwang Yang, David J. Venzon, Seong Jin Kim, Ronald E. Gress

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Although graft-versus-leukemia effects in allogeneic bone marrow transplantation (alloBMT) are well documented, graft-versus-tumor (GVT) effects are poorly defined. To investigate the latter, we established a murine model of breast cancer using TS/A, a transforming growth factor (TGF)-β1-secreting breast cancer cell line of BALB/c origin. In the setting of disparate (parent into F1) alloBMT, no appreciable GVT was identified. To assess whether TGF-β1 secreted by the tumor might inhibit the antitumor response, TGF-β1 antisense vector was transfected into the TS/A breast cancer cell line. Mice were inoculated with either TGF-β1 antisense transfected or the mock transfected cell line and underwent syngeneic or alloBMT. No evidence of GVT was appreciated for the mock-transfected breast cancer cell line as assessed by an absence of a statistically significant difference in survival between syngeneic and alloBMT groups. However, there was a highly statistically significant survival difference between allogeneic versus syngeneic bone marrow transplantation groups inoculated with the TGF-β1 antisense-transfected cell line (P = .00001) as well as when comparing the survival of mice that received alloBMT for TGF-β1 antisense-transfected tumor versus mock-transfected tumor (P = .0008). These data suggest that (1) GVT exists against the antisense-transfected breast cancer cells in this experimental model and (2) TGF-β1 may be involved in suppressing antitumor responses in the setting of alloBMT for breast cancer.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume7
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Breast cancer
  • Graft-versus-tumor
  • TGF-Β1

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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