TY - JOUR
T1 - Human chorionic gonadotropin inhibits Kaposi's sarcoma associated angiogenesis, matrix metalloprotease activity, and tumor growth
AU - Pfeffer, Ulrich
AU - Bisacchi, Davide
AU - Morini, Monica
AU - Benelli, Roberto
AU - Minghelli, Simona
AU - Vacca, Angelo
AU - Noonan, Douglas M.
AU - Albini, Adriana
PY - 2002
Y1 - 2002
N2 - Kaposi's sarcoma is a highly angiogenic, AIDS-associated neoplasm that is more frequent in male than in female patients. Cases of spontaneous regression during pregnancy have been reported and the pregnancy hormone human chorionic gonadotropin (hCG) has shown anti-Kaposi's sarcoma activity in several, but not all, clinical trials. Antiproliferative and proapoptotic activities specific for Kaposi's sarcoma (KS) cells have been shown. We report here further analyses of the anti-KS activity of the hormone and show that urinary hCG, the hCG β-subunit, the hCG β-core, and to a lesser extent a recombinant hCG, directly inhibit the activity of matrix metalloproteases of different origin. The hCG hormone also inhibited angiogenesis in vivo in the matrigel sponge assay as well as growth of KS cell xenografts in nude mice. The effect of the pure recombinant hormone dimer on xenograft growth was transient, indicating that the activity of intact hCG alone is not sufficient to overcome the growth potential of this tumor and suggesting that active hCG fragments or other anti-KS activities contribute to the activity of urinary hCG.
AB - Kaposi's sarcoma is a highly angiogenic, AIDS-associated neoplasm that is more frequent in male than in female patients. Cases of spontaneous regression during pregnancy have been reported and the pregnancy hormone human chorionic gonadotropin (hCG) has shown anti-Kaposi's sarcoma activity in several, but not all, clinical trials. Antiproliferative and proapoptotic activities specific for Kaposi's sarcoma (KS) cells have been shown. We report here further analyses of the anti-KS activity of the hormone and show that urinary hCG, the hCG β-subunit, the hCG β-core, and to a lesser extent a recombinant hCG, directly inhibit the activity of matrix metalloproteases of different origin. The hCG hormone also inhibited angiogenesis in vivo in the matrigel sponge assay as well as growth of KS cell xenografts in nude mice. The effect of the pure recombinant hormone dimer on xenograft growth was transient, indicating that the activity of intact hCG alone is not sufficient to overcome the growth potential of this tumor and suggesting that active hCG fragments or other anti-KS activities contribute to the activity of urinary hCG.
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U2 - 10.1210/en.143.8.3114
DO - 10.1210/en.143.8.3114
M3 - Article
C2 - 12130577
AN - SCOPUS:0036321006
VL - 143
SP - 3114
EP - 3121
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 8
ER -