Prothymosin alpha augments deficient antitumor activity of monocytes from melanoma patients in vitro.
Human peripheral blood monocytes derived from normal donors, melanoma patients (MP) before and after chemotherapy (MPa) were assayed for their capacity to inhibit SK-MEL-28 melanoma cell growth in vitro; in addition, growth modulating effects by prothymosin alpha 1 (ProTa) were studied. After preincubation with or without ProTa for 1 day, monocytes were cultured in the absence or presence of interferon-gamma (rIFN-gamma) for a further day, and after cocultivation with SK-MEL-28 melanoma cells for 3 days monocyte/macrophage-mediated tumoristatic activity was determined employing the microculture tetrazolium (MTT) assay. The level of baseline growth inhibitory activity of unstimulated MP and MPa monocytes was 22% and 15%, respectively, and was significantly lower (p < 0.001) than that of normal monocytes (35%). The stimulation of monocytes/macrophages by rIFN-gamma greatly elevated the mean of their antitumor activity up to 44%, 49% and 58% in the group of MP, MPa and normal donors, respectively. ProTa significantly increased the level of monocyte-mediated growth inhibition of MP and normal donors, when it was applied alone or in combination with rIFN-gamma. Monocytes of MP at early stages (I and II) of their disease, when incubated with rIFN-gamma, showed a higher increase in tumoristatic activity than at stage III and tended to be the most susceptible to preincubation with ProTa followed by rIFN-gamma activation. However, on average tumoristatic activity of MP/MPa monocytes was significantly lower compared with that of normal monocytes, when activated with rIFN-gamma or ProTa alone or combined. Moreover, no effects on TNF-alpha secretion of MP/MPa monocytes were found by ProTa and/or rIFN-gamma, whereas TNF-alpha levels from normal monocytes were significantly increased by the two stimuli. These results indicate that monocyte disorders in melanoma patients may be partially normalized by ProTa.
Garbin
F
F
Institut für Pharmazie, Freien Universität Berlin.
Eckert
K
K
Büttner
P
P
Garbe
C
C
Maurer
H R
HR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002450:Cell Communication; D002455:Cell Division; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000097:blood* / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D011498:Protein Precursors / Q000494:pharmacology*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin