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Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 1038-1044
Antineoplastic Urinary Protein Inhibits Kaposi's Sarcoma and
Angiogenesis In Vitro and In Vivo
Rizwan Masood,
Megan E. McGarvey,
Tong Zheng,
Jie Cai,
Naveen Arora,
D. Lynne Smith,
Nathan Sloane, and
Parkash S. Gill
From the University of Southern California School of Medicine, the
Department of Internal Medicine and Pathology, Los Angeles, CA; the
Centre for Biomedical Technology, Delhi, India; and Antitumor Research
Products, Inc, Germantown, TN.
Kaposi's sarcoma (KS) is the most common tumor in human
immunodeficiency virus infection and acquired immune deficiency
syndrome. Recent clinical trials with human chorionic gonadotropin
(hCG) prepared from early pregnancy urine have shown encouraging
results in the resolution of KS lesions. A urinary protein with
antitumor activity, ANUP (antineoplastic urinary protein), a dimer of
32 kD, has previously been shown to inhibit the growth of various tumor
cell lines in vivo. It was thus studied for its activity in KS cell
lines in vitro and in vivo to determine whether it could be a source of
the anti-KS activity observed in hCG preparations. ANUP is a strong
growth inhibitor for KS cell lines, but has little or no effect on
fibroblast, aortic smooth muscle, T- and B-lymphocyte, and monocyte
cell lines. ANUP also inhibited the proliferation of endothelial cell
lines, suggesting that the in vitro effects were endothelial cell
lineage-specific. However, ANUP antibodies did not block the
inhibitory effect of certain commercial preparations of hCG, previously
shown to be active in KS. Thus, the active protein in these commercial
preparations of hCG may be distinct from ANUP. The antitumor activity
of ANUP was further confirmed in a chicken allantoic membrane (CAM)
assay in which vascular endothelial growth factor (VEGF) and beta
fibroblast growth factor (bFGF)-induced angiogenesis was
inhibited by ANUP in a dose-dependent manner. In vivo activity of ANUP
was demonstrated in the murine model of KS, where ANUP inhibited tumor
growth. ANUP is thus a potential candidate for development in the
treatment of KS and other diseases in which angiogenesis plays an
important role.
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