Characterization of a novel tumor-derived cytokine

Endothelial-monocyte activating polypeptide II

Janet Kao, Keith Houck, Yan Fan, Iris Haehnel, Steven K. Libutti, Mark L. Kayton, Tracy Grikscheit, John Chabot, Roman Nowygrod, Steven Greenberg, Wun Jing Kuang, David W. Leung, Joanne R. Hayward, Walter Kisiel, Mark Heath, Jerold Brett, David M. Stern

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Endothelial-monocyte activating polypeptide II (EMAP II) was initially identified in the supernatant of murine methylcholanthrene A-induced fibrosarcomas (Meth A) by its capacity to activate host effector cells (Kao, J., Ryan, J., Brett, J., Chen, J., Shen, H., Fan, Y-G., Godman, G., Familletti, P., Wang, F., Pan, Y-C., Stern, D., and Clauss, M. (1992) J. Biol. Chem. 267, 20239-20247). Based on the NH2-terminal protein sequence, a full-length cDNA has been cloned which indicates that the precursor of EMAP II is a unique, leaderless, single polypeptide chain with predicted molecular mass ≈34 kDa and that the mature form released by Meth A cells corresponds to ≈20 kDa. Purified recombinant mature EMAP II (EMAP II, ≈20 kDa form) activated endothelial cells with resulting elevation of cytosolic free calcium concentration, release of von Willebrand factor, induction of tissue factor, and expression of the adhesion molecules E-selectin and P-selectin. Neutrophils exposed to EMAP II demonstrated elevated cytosolic free calcium concentration, peroxidase generation, and chemotaxis. EMAP II also activated mononuclear phagocytes elevating cytosolic free calcium concentration, inducing tumor necrosis factor-α (TNF) and tissue factor, and stimulating chemotaxis. Systemic infusion of EMAP II into C3H/HeJ or Balb/c mice was associated with systemic toxicity, pulmonary congestion, and the appearance of TNF, interleukin-1 and -6 in the plasma. A single intra-tumor injection of EMAP II into Meth A sarcomas induced acute thrombohemorrhage and partial tumor regression. Local injection of EMAP II into a tumor resistant to the effects of TNF, murine mammary carcinoma, rendered it sensitive to subsequently administered TNF, which resulted in acute thrombohemorrhage and partial regression. These data suggest that recombinant EMAP II, a tumor-derived cytokine, has properties of a proinflammatory mediator with the capacity to prime the tumor vasculature for a locally destructive process.

Original languageEnglish (US)
Pages (from-to)25106-25119
Number of pages14
JournalJournal of Biological Chemistry
Volume269
Issue number40
StatePublished - Oct 7 1994
Externally publishedYes

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Tumors
Cytokines
Neoplasms
Methylcholanthrene
Fibrosarcoma
Tumor Necrosis Factor-alpha
Thromboplastin
Chemotaxis
Calcium
small inducible cytokine subfamily E, member 1
Injections
P-Selectin
E-Selectin
Endothelial cells
von Willebrand Factor
Molecular mass
Phagocytes
Interleukin-1
Sarcoma
Peroxidase

ASJC Scopus subject areas

  • Biochemistry

Cite this

Kao, J., Houck, K., Fan, Y., Haehnel, I., Libutti, S. K., Kayton, M. L., ... Stern, D. M. (1994). Characterization of a novel tumor-derived cytokine: Endothelial-monocyte activating polypeptide II. Journal of Biological Chemistry, 269(40), 25106-25119.

Characterization of a novel tumor-derived cytokine : Endothelial-monocyte activating polypeptide II. / Kao, Janet; Houck, Keith; Fan, Yan; Haehnel, Iris; Libutti, Steven K.; Kayton, Mark L.; Grikscheit, Tracy; Chabot, John; Nowygrod, Roman; Greenberg, Steven; Kuang, Wun Jing; Leung, David W.; Hayward, Joanne R.; Kisiel, Walter; Heath, Mark; Brett, Jerold; Stern, David M.

In: Journal of Biological Chemistry, Vol. 269, No. 40, 07.10.1994, p. 25106-25119.

Research output: Contribution to journalArticle

Kao, J, Houck, K, Fan, Y, Haehnel, I, Libutti, SK, Kayton, ML, Grikscheit, T, Chabot, J, Nowygrod, R, Greenberg, S, Kuang, WJ, Leung, DW, Hayward, JR, Kisiel, W, Heath, M, Brett, J & Stern, DM 1994, 'Characterization of a novel tumor-derived cytokine: Endothelial-monocyte activating polypeptide II', Journal of Biological Chemistry, vol. 269, no. 40, pp. 25106-25119.
Kao J, Houck K, Fan Y, Haehnel I, Libutti SK, Kayton ML et al. Characterization of a novel tumor-derived cytokine: Endothelial-monocyte activating polypeptide II. Journal of Biological Chemistry. 1994 Oct 7;269(40):25106-25119.
Kao, Janet ; Houck, Keith ; Fan, Yan ; Haehnel, Iris ; Libutti, Steven K. ; Kayton, Mark L. ; Grikscheit, Tracy ; Chabot, John ; Nowygrod, Roman ; Greenberg, Steven ; Kuang, Wun Jing ; Leung, David W. ; Hayward, Joanne R. ; Kisiel, Walter ; Heath, Mark ; Brett, Jerold ; Stern, David M. / Characterization of a novel tumor-derived cytokine : Endothelial-monocyte activating polypeptide II. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 40. pp. 25106-25119.
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AU - Greenberg, Steven

AU - Kuang, Wun Jing

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