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Human Chorionic Gonadotropin Inhibits Kaposi’s Sarcoma Associated Angiogenesis, Matrix Metalloprotease Activity, and Tumor Growth

Laboratory of Molecular Biology (U.P., D.B., R.B., S.M., A.A.) and Tumor Progression Section (M.M., D.M.N.), National Cancer Research Institute Genova, c/o Advanced Biotechnology Center Genova, Genova 16132, Italy; and Department of Biomedical Sciences and Human Oncology (A.V.), University of Bari, Bari 70124, Italy

Address all correspondence and requests for reprints to: Adriana Albini, Laboratory of Molecular Biology, National Cancer Research Institute Genoa, Largo Rosanna Benzi 10, 16132 Genova, Italy. E-mail: . albini{at}cba.unige.it

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 ß-subunit, the hCG ß-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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