Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin.
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.
Lang
M E
ME
Institute of General & Experimental Pathology, University of Innsbruck, Austria.
Lottersberger
C
C
Roth
B
B
Böck
G
G
Recheis
H
H
Sgonc
R
R
Stürzl
M
M
Albini
A
A
Tschachler
E
E
Zangerle
R
R
Donini
S
S
Feichtinger
H
H
Schwarz
S
S
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
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