title: Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin.
abstract: OBJECTIVE
  Elucidation of the mechanisms of the previously shown growth-inhibitory action of human chorionic gonadotropin (hCG) on Kaposi's sarcoma (KS) cells and the role of the luteinizing hormone/hCG receptor (hCGR).
  
  
  METHODS
  Analysis of KS tissues and cultured spindle-type KS cells for the presence of the hCGR using 125I-hCG binding and reverse transcriptase-polymerase chain reaction; analysis of several hCG preparations (urinary, recombinant, isolated alpha and beta subunits); analysis of apoptosis mechanisms by several assays including using z-Val-Ala-Asp-fluoromethylketone (zVAD-FMK), a known apoptosis-inhibitory drug.
  
  
  RESULTS
  First, we found that some urinary preparations of hCG (e.g., CG-10, Steris Profasi) were indeed KS-killing but others (such as Pregnyl, Choragon, Serono Profasi) were not. Secondly, recombinant subunits (alpha as well as beta) of hCG were KS cell-killing but recombinant intact hCG was not. Thirdly, the hCGR message and protein were undetectable in KS. Fourthly, CG10-induced cell death occurred by apoptosis and KS cells could be rescued by preincubation with zVAD-FMK. Finally, we also found that normal peripheral blood lymphocytes (PBL) were killed by CG-10.
  
  
  CONCLUSIONS
  It is proposed that the action of subunits or subunit fragments of hCG, mediated by a putative orphan receptor (as opposed to the hCGR) and executed by interleukin-1-converting enzyme (ICE)-like protease(s), constitutes a novel apoptosis mechanism effective towards KS cells, but PBLs and possibly other cells as well. These results provide a basis for testing in vitro the therapeutic efficacy of hCG preparations which, in turn, should improve current clinical trials with 'hCG' in patients who have KS.
authors.affiliation: Institute of General & Experimental Pathology, University of Innsbruck, Austria.
authors.forename: M E
authors.initials: ME
authors.lastname: Lang
authors.forename: C
authors.initials: C
authors.lastname: Lottersberger
authors.forename: B
authors.initials: B
authors.lastname: Roth
authors.forename: G
authors.initials: G
authors.lastname: Böck
authors.forename: H
authors.initials: H
authors.lastname: Recheis
authors.forename: R
authors.initials: R
authors.lastname: Sgonc
authors.forename: M
authors.initials: M
authors.lastname: Stürzl
authors.forename: A
authors.initials: A
authors.lastname: Albini
authors.forename: E
authors.initials: E
authors.lastname: Tschachler
authors.forename: R
authors.initials: R
authors.lastname: Zangerle
authors.forename: S
authors.initials: S
authors.lastname: Donini
authors.forename: H
authors.initials: H
authors.lastname: Feichtinger
authors.forename: S
authors.initials: S
authors.lastname: Schwarz
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis; D005434:Flow Cytometry; D006062:Gonadotropins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D015658:HIV Infections / Q000150:complications; D015497:HIV-1; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000652:urine; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C042918:CG 10; D006062:Gonadotropins; D012333:RNA, Messenger; D011974:Receptors, LH; D011994:Recombinant Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D001613:beta 2-Microglobulin