In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-α is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII)

Peter C. Wu, H. Richard Alexander, James Huang, Patrick Hwu, Michael Gnant, Adam C. Berger, Ewa Turner, Olga Wilson, Steven K. Libutti

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF)-α is a potent anticancer agent that seems to selectively target tumor-associated vasculature resulting in hemorrhaging necrosis of tumors without injury to surrounding tissues. The major limitation in the clinical use of TNF has been severe dose-limiting toxicity when administered systematically. However, when administered in isolated organ perfusion it results in regression of advanced bulk tumors. A better understanding of the mechanisms of TNF-induced antitumor effects may provide valuable information into how its clinical use in cancer treatment may be expanded. We describe here that the release of a novel tumor-derived cytokine endothelial-monocyte-activating polypeptide II (EMAPII) renders the tumor- associated vasculature sensitive to TNF. EMAPII has the unique ability to induce tissue factor production by tumor vascular endothelial cells that initiates thrombogenic cascades, which may play a role in determining tumor sensitivity to TNF. We demonstrate here that constitute overexpression of EMAPII in a TNF-resistant human melanoma line by retroviral-mediated transfer of EMAPII cDNA renders the tumor sensitive to the effects of systemic TNF in vivo, but not in vitro. This interaction between tumors and their associated neovasculature provides an explanation for the focal effects of TNF on tumors and possibly for the variable sensitivity of tumors to bioactive agents.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalCancer Research
Volume59
Issue number1
StatePublished - Jan 1 1999
Externally publishedYes

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Melanoma
Tumor Necrosis Factor-alpha
Cytokines
Neoplasms
small inducible cytokine subfamily E, member 1
Thromboplastin
Antineoplastic Agents
Necrosis
Endothelial Cells
Complementary DNA
Perfusion
Wounds and Injuries

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-α is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII). / Wu, Peter C.; Alexander, H. Richard; Huang, James; Hwu, Patrick; Gnant, Michael; Berger, Adam C.; Turner, Ewa; Wilson, Olga; Libutti, Steven K.

In: Cancer Research, Vol. 59, No. 1, 01.01.1999, p. 205-212.

Research output: Contribution to journalArticle

Wu, PC, Alexander, HR, Huang, J, Hwu, P, Gnant, M, Berger, AC, Turner, E, Wilson, O & Libutti, SK 1999, 'In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-α is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII)', Cancer Research, vol. 59, no. 1, pp. 205-212.
Wu, Peter C. ; Alexander, H. Richard ; Huang, James ; Hwu, Patrick ; Gnant, Michael ; Berger, Adam C. ; Turner, Ewa ; Wilson, Olga ; Libutti, Steven K. / In vivo sensitivity of human melanoma to tumor necrosis factor (TNF)-α is determined by tumor production of the novel cytokine endothelial-monocyte activating polypeptide II (EMAPII). In: Cancer Research. 1999 ; Vol. 59, No. 1. pp. 205-212.
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