title: Prothymosin alpha augments deficient antitumor activity of monocytes from melanoma patients in vitro.
abstract: 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.
authors.affiliation: Institut für Pharmazie, Freien Universität Berlin.
authors.forename: F
authors.initials: F
authors.lastname: Garbin
authors.forename: K
authors.initials: K
authors.lastname: Eckert
authors.forename: P
authors.initials: P
authors.lastname: Büttner
authors.forename: C
authors.initials: C
authors.lastname: Garbe
authors.forename: H R
authors.initials: HR
authors.lastname: Maurer
mesh_terms: 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
chemical_list: D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin