Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin

Monika E. Lang, Clemens Lottersberger, Birgit Roth, Günther Böck, Heidrun Recheis, Roswitha Sgonc, Michael Stürzl, Adriana Albini, Erwin Tschachler, Robert Zangerle, Silvia Donini, Hans Feichtinger, Siegfried Schwarz

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)1333-1340
Number of pages8
JournalAIDS (London, England)
Volume11
Issue number11
Publication statusPublished - 1997

Fingerprint

Kaposi's Sarcoma
Chorionic Gonadotropin
Cell Culture Techniques
Apoptosis
LH Receptors
Caspase 1
Luteinizing Hormone
Reverse Transcriptase Polymerase Chain Reaction
Sarcoma
Peptide Hydrolases
Cell Death
Clinical Trials
Lymphocytes
Growth

Keywords

  • Apoptosis
  • Human chorionic gonadotropin
  • Kaposi's sarcoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lang, M. E., Lottersberger, C., Roth, B., Böck, G., Recheis, H., Sgonc, R., ... Schwarz, S. (1997). Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin. AIDS (London, England), 11(11), 1333-1340.

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 journalArticle

Lang, ME, Lottersberger, C, Roth, B, Böck, G, Recheis, H, Sgonc, R, Stürzl, M, Albini, A, Tschachler, E, Zangerle, R, Donini, S, Feichtinger, H & Schwarz, S 1997, 'Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin', AIDS (London, England), vol. 11, no. 11, pp. 1333-1340.
Lang ME, Lottersberger C, Roth B, Böck G, Recheis H, Sgonc R et al. Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin. AIDS (London, England). 1997;11(11):1333-1340.
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. / Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin. In: AIDS (London, England). 1997 ; Vol. 11, No. 11. pp. 1333-1340.
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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.",
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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

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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.

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