Human chorionic gonadotropin inhibits Kaposi's sarcoma associated angiogenesis, matrix metalloprotease activity, and tumor growth.
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 beta-subunit, the hCG beta-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.
Laboratory of Molecular Biology, National Cancer Research Institute Genova, c/o Advanced Biotechnology Center Genova, Large Rosanna Benzi 10, Genoa 16132, Italy.
Ulrich
U
Pfeffer
Davide
D
Bisacchi
Monica
M
Morini
Roberto
R
Benelli
Simona
S
Minghelli
Angelo
A
Vacca
Douglas M
DM
Noonan
Adriana
A
Albini
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000494:pharmacology; D012514:Sarcoma, Kaposi / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D014407:Tumor Cells, Cultured
D006063:Chorionic Gonadotropin; D061965:Matrix Metalloproteinase Inhibitors; D021122:Protein Subunits; D011994:Recombinant Proteins