Improved antitumor response to isolated limb perfusion with tumor necrosis factor after upregulation of endothelial monocyte-activating polypeptide II in soft tissue sarcoma

T. E. Lans, T. L M Ten Hagen, R. Van Horssen, P. C. Wu, S. T. Van Tiel, S. K. Libutti, H. R. Alexander, A. M M Eggermont

Research output: Contribution to journalArticle

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Abstract

Background: Experiments with tumor necrosis factor α (TNF) in rodents have shown that a high dose can lead to hemorrhagic necrosis in tumors. Endothelial monocyte-activating polypeptide II (EMAP-II) is a novel tumor-derived cytokine, and its expression increases the TNF-1 receptor on tumor endothelium, enhances the induction of tissue factor on tumor endothelial cells, and has an antiangiogenic effect. It has recently been shown that in vivo sensitivity of tumor vasculature to TNF is determined by tumor production of EMAP-II. Methods: We measured the level of EMAP-II in a TNF-resistant soft tissue sarcoma. We subsequently stabile-transfected this cell line with a retroviral construct containing the EMAP gene. In an extremity perfusion model in tumor-bearing rats, we measured response rates to TNF therapy. Results: Functional EMAP-II production was increased after this transfection. Immunostaining of paraffin-embedded tumor tissue sections in rats showed an overexpression of human EMAP-II. Results of the TNF perfusions in rats suggest that this tumor is more sensitive to TNF therapy. Conclusions: EMAP-II is produced in various levels. One can increase the sensitivity of tumor for TNF therapy in vivo by upregulating the EMAP-II production. This result leaves an opportunity for enhanced TNF response of tumors in future settings.

Original languageEnglish (US)
Pages (from-to)812-819
Number of pages8
JournalAnnals of Surgical Oncology
Volume9
Issue number8
DOIs
StatePublished - Oct 2002
Externally publishedYes

Fingerprint

Sarcoma
Up-Regulation
Extremities
Tumor Necrosis Factor-alpha
Perfusion
Neoplasms
small inducible cytokine subfamily E, member 1
Tumor Necrosis Factor Receptors
Thromboplastin
Paraffin
Endothelium
Transfection
Rodentia
Necrosis
Therapeutics
Endothelial Cells
Cytokines
Cell Line

Keywords

  • EMAP-II
  • Limb perfusion
  • Sarcoma
  • TNF

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Improved antitumor response to isolated limb perfusion with tumor necrosis factor after upregulation of endothelial monocyte-activating polypeptide II in soft tissue sarcoma. / Lans, T. E.; Hagen, T. L M Ten; Van Horssen, R.; Wu, P. C.; Van Tiel, S. T.; Libutti, S. K.; Alexander, H. R.; Eggermont, A. M M.

In: Annals of Surgical Oncology, Vol. 9, No. 8, 10.2002, p. 812-819.

Research output: Contribution to journalArticle

Lans, T. E. ; Hagen, T. L M Ten ; Van Horssen, R. ; Wu, P. C. ; Van Tiel, S. T. ; Libutti, S. K. ; Alexander, H. R. ; Eggermont, A. M M. / Improved antitumor response to isolated limb perfusion with tumor necrosis factor after upregulation of endothelial monocyte-activating polypeptide II in soft tissue sarcoma. In: Annals of Surgical Oncology. 2002 ; Vol. 9, No. 8. pp. 812-819.
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AU - Wu, P. C.

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AU - Alexander, H. R.

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