Identification of interleukin-1 and platelet-derived growth factor-B as major mitogens for the spindle cells of Kaposi's sarcoma: a combined in vitro and in vivo analysis.
By means of a combined in vitro and in vivo analysis we provide evidence that IL-1 beta and PDGF-B, but not OSM (oncostatin M) or IL-6, are major mitogens for the spindle cells of Kaposi's sarcoma (KS) in vivo. PDGF-B and IL-1 beta stimulated proliferation of cultivated KS spindle cells in vitro. Analysis of gene expression in vivo revealed that both factors as well as the PDGF beta-receptor are present in KS lesions. By contrast, IL-6 had no effect and OSM inhibited proliferation of cultivated KS spindle cells. Again, the effect of these factors on cultivated KS spindle cells in vitro was reflected by the gene expression observed in KS lesions in vivo. Neither the expression of IL-6 receptor nor of OSM could be detected in KS lesions by in situ hybridization. Moreover, in situ hybridization revealed an identical pattern of gene expression in cultivated KS spindle cells and KS spindle cells in vivo with respect to the above-mentioned cytokines [PDGF-B, IL-1 beta, IL-1 alpha, IL-6, OSM] and their receptors [PDGF beta-receptor, gp130, IL-6 receptor, leukemia inhibitory factor (LIF) receptor]. This further supported the suitability of cultivated KS spindle cells as an in vitro model in order to determine which cytokines may activate proliferation of KS spindle cells in vivo.
Stürzl
M
M
Abteilung Virusforschung, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Brandstetter
H
H
Zietz
C
C
Eisenburg
B
B
Raivich
G
G
Gearing
D P
DP
Brockmeyer
N H
NH
Hofschneider
P H
PH
D002455:Cell Division / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000032:analysis* / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis*; D008297:Male; D053683:Oncostatin M; D010455:Peptides / Q000032:analysis* / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000032:analysis* / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D018121:Receptors, Cytokine / Q000032:analysis; D018123:Receptors, Interleukin / Q000032:analysis; D019947:Receptors, Interleukin-6; D053677:Receptors, Oncostatin M; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis; D012514:Sarcoma, Kaposi / Q000737:chemistry / Q000473:pathology*
D007375:Interleukin-1; D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D053677:Receptors, Oncostatin M; D053683:Oncostatin M; D017479:Receptors, Platelet-Derived Growth Factor