Post-transplantation malignancy: a cell autonomous mechanism with implications for therapy. Academic Article uri icon

Overview

MeSH Major

  • Neoplasms
  • Organ Transplantation

abstract

  • Malignancy is a dreaded complication following organ transplantation. Immunosuppressive therapy-induced impairment of the host immune system is the prevailing hypothesis for the high incidence and aggressive progression of post-transplant neoplasm. We summarize our observations supporting an autonomous cellular mechanism for cyclosporine and tacrolimus associated metastases. Cyclosporine conferred tumor invasiveness by a direct effect on the tumor cells and promoted metastases in T-, B-, and NK cell deficient SCID- beige mice, and anti-TGF-beta antibodies reduced metastases. Tacrolimus, another calcineurin inhibitor widely used in transplantation, induced TGF-beta secretion by tumor cells and promoted metastases in the SCID- beige mice. The immunosuppressive macrolide rapamycin reversed an invasive phenotype to a non-invasive one, reduced circulating levels of TGF-beta1 and prevented tumor growth and metastases in the immocompetant BALB/c mice and in the SCID-beige mice. Our studies, in addition to demonstrating a cell autonomous mechanism for tumor progression, advance TGF-beta blockade as an anti-tumor strategy.

publication date

  • December 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2744527

PubMed ID

  • 19768190

Additional Document Info

start page

  • 369

end page

  • 88

volume

  • 120