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Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells.

Schwarz MA, Kandel J, Brett J, Li J, Hayward J, Schwarz RE, Chappey O, Wautier JL, Chabot J, Lo Gerfo P, Stern D - J. Exp. Med. (1999)

Bottom Line: Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001).In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected.These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York 10032, USA. mschwarz@chla.usc.edu

ABSTRACT
Neovascularization is essential for growth and spread of primary and metastatic tumors. We have identified a novel cytokine, endothelial-monocyte activating polypeptide (EMAP) II, that potently inhibits tumor growth, and appears to have antiangiogenic activity. Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001). Neovascularization of the mouse cornea was similarly prevented by EMAP II (P < 0.003). Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume of 65% versus controls (P < 0.003). Tumors from human breast carcinoma-derived MDA-MB 468 cells were suppressed by >80% in EMAP II-treated animals (P < 0.005). In a lung metastasis model, EMAP II blocked outgrowth of Lewis lung carcinoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, approximately 80% were inhibited with maximum diameter <2 mm (P < 0.002 vs. controls). In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.

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Disappearance of 125I-EMAP II from mouse plasma after intravenous (□) or intraperitoneal (▪) infusion. Mice received 125I-EMAP II (0.26 μg/ml) by either intravenous or intraperitoneal injection, and plasma was sampled at the indicated time points. The method for data fitting and parameters of clearance are described in the text.
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Figure 4: Disappearance of 125I-EMAP II from mouse plasma after intravenous (□) or intraperitoneal (▪) infusion. Mice received 125I-EMAP II (0.26 μg/ml) by either intravenous or intraperitoneal injection, and plasma was sampled at the indicated time points. The method for data fitting and parameters of clearance are described in the text.

Mentions: To perform further in vivo studies with rEMAP II, its plasma clearance was evaluated. Clearance studies were performed using either intravenously or intraperitoneally administered 125I-rEMAP II (Fig. 4). The fall in plasma concentration of 125I-rEMAP II after intravenous injection best fit a biexponential function 18; the distribution and elimination half-lives were 0.47 ± 0.17 and 103 ± 5 min, respectively. After intraperitoneal injection, 125I-EMAP II was detected in plasma after 1 min, and the maximum concentration was reached by 35 ± 10 min. The resorption phase of rEMAP II handling in vivo was best described as a first-order process. The elimination phase after intraperitoneal administration fit to a monoexponential decline, and the resorption and elimination half-lives were 50.1 ± 0.1 and 102 ± 6 min, respectively.


Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells.

Schwarz MA, Kandel J, Brett J, Li J, Hayward J, Schwarz RE, Chappey O, Wautier JL, Chabot J, Lo Gerfo P, Stern D - J. Exp. Med. (1999)

Disappearance of 125I-EMAP II from mouse plasma after intravenous (□) or intraperitoneal (▪) infusion. Mice received 125I-EMAP II (0.26 μg/ml) by either intravenous or intraperitoneal injection, and plasma was sampled at the indicated time points. The method for data fitting and parameters of clearance are described in the text.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195582&req=5

Figure 4: Disappearance of 125I-EMAP II from mouse plasma after intravenous (□) or intraperitoneal (▪) infusion. Mice received 125I-EMAP II (0.26 μg/ml) by either intravenous or intraperitoneal injection, and plasma was sampled at the indicated time points. The method for data fitting and parameters of clearance are described in the text.
Mentions: To perform further in vivo studies with rEMAP II, its plasma clearance was evaluated. Clearance studies were performed using either intravenously or intraperitoneally administered 125I-rEMAP II (Fig. 4). The fall in plasma concentration of 125I-rEMAP II after intravenous injection best fit a biexponential function 18; the distribution and elimination half-lives were 0.47 ± 0.17 and 103 ± 5 min, respectively. After intraperitoneal injection, 125I-EMAP II was detected in plasma after 1 min, and the maximum concentration was reached by 35 ± 10 min. The resorption phase of rEMAP II handling in vivo was best described as a first-order process. The elimination phase after intraperitoneal administration fit to a monoexponential decline, and the resorption and elimination half-lives were 50.1 ± 0.1 and 102 ± 6 min, respectively.

Bottom Line: Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001).In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected.These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York 10032, USA. mschwarz@chla.usc.edu

ABSTRACT
Neovascularization is essential for growth and spread of primary and metastatic tumors. We have identified a novel cytokine, endothelial-monocyte activating polypeptide (EMAP) II, that potently inhibits tumor growth, and appears to have antiangiogenic activity. Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001). Neovascularization of the mouse cornea was similarly prevented by EMAP II (P < 0.003). Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume of 65% versus controls (P < 0.003). Tumors from human breast carcinoma-derived MDA-MB 468 cells were suppressed by >80% in EMAP II-treated animals (P < 0.005). In a lung metastasis model, EMAP II blocked outgrowth of Lewis lung carcinoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, approximately 80% were inhibited with maximum diameter <2 mm (P < 0.002 vs. controls). In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.

Show MeSH
Related in: MedlinePlus