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Prothymosin alpha augments deficient antitumor activity of monocytes from melanoma patients in vitro

Garbin, F.; Eckert, K.; Büttner, P.; Garbe, C.; Maurer, H.R.

Anticancer Research 14(6b): 2405-2411

1994

ISSN/ISBN: 0250-7005
PMID: 7872660
Document Number: 430229
Human peripheral blood monocytes derived from normal donors, melanoma patients (MP) before and after chemotherapy (MP-alpha) were assayed for their capacity to inhibit SK-MEL-28 melanoma cell growth in vitro; in addition, growth modulating effects by prothymosin alpha-1 (ProT-alpha) were studied. After preincubation with or without ProT-alpha 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 MP-alpha monocytes was 22% and 15%, respectively, and was significantly lower (p lt 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, MP-alpha and normal donors, respectively. ProT-alpha 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/MP-alpha monocytes was significantly lower compared with that of normal monocytes, when activated with rIFN-gamma or ProT-alpha alone or combined. Moreover, no effects on TNF-alpha secretion of MP/MP-alpha 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 ProT-alpha.

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