Abstract
Objectives: 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). Design and methods: Analysis of KS tissues and cultured spindle-type KS cells for the presence of the hCCR using 125I-hCC binding and reverse transcriptase-polymerase chain reaction; analysis of several hCC preparations (urinary, recombinant, isolated α and β 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 (α as well as β) 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. Conclusion: 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1333-1340 |
| Number of pages | 8 |
| Journal | AIDS (London, England) |
| Volume | 11 |
| Issue number | 11 |
| Publication status | Published - 1997 |
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Keywords
- Apoptosis
- Human chorionic gonadotropin
- Kaposi's sarcoma
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin. / Lang, Monika E.; Lottersberger, Clemens; Roth, Birgit; Böck, Günther; Recheis, Heidrun; Sgonc, Roswitha; Stürzl, Michael; Albini, Adriana; Tschachler, Erwin; Zangerle, Robert; Donini, Silvia; Feichtinger, Hans; Schwarz, Siegfried.
In: AIDS (London, England), Vol. 11, No. 11, 1997, p. 1333-1340.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin
AU - Lang, Monika E.
AU - Lottersberger, Clemens
AU - Roth, Birgit
AU - Böck, Günther
AU - Recheis, Heidrun
AU - Sgonc, Roswitha
AU - Stürzl, Michael
AU - Albini, Adriana
AU - Tschachler, Erwin
AU - Zangerle, Robert
AU - Donini, Silvia
AU - Feichtinger, Hans
AU - Schwarz, Siegfried
PY - 1997
Y1 - 1997
N2 - Objectives: 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). Design and methods: Analysis of KS tissues and cultured spindle-type KS cells for the presence of the hCCR using 125I-hCC binding and reverse transcriptase-polymerase chain reaction; analysis of several hCC preparations (urinary, recombinant, isolated α and β 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 (α as well as β) 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. Conclusion: 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.
AB - Objectives: 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). Design and methods: Analysis of KS tissues and cultured spindle-type KS cells for the presence of the hCCR using 125I-hCC binding and reverse transcriptase-polymerase chain reaction; analysis of several hCC preparations (urinary, recombinant, isolated α and β 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 (α as well as β) 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. Conclusion: 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.
KW - Apoptosis
KW - Human chorionic gonadotropin
KW - Kaposi's sarcoma
UR - http://www.scopus.com/inward/record.url?scp=9844227347&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9844227347&partnerID=8YFLogxK
M3 - Article
C2 - 9302442
AN - SCOPUS:9844227347
VL - 11
SP - 1333
EP - 1340
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 11
ER -