INHIBITION OF MELANOMA PULMONARY METASTASIS BY METHYLXANTHINES DUE TODECREASED INVASION AND PROLIFERATION

Theophylline- and caffeine-treated B16-F10 cells exhibited low adhesio n to laminin/collagen type IV and reduced invasion through Matrigel in an in vitro assay. In contrast, theobromine appeared ineffective. Whe n young adult C57BL/6 mice were injected intravenously with theophylli ne-treated B16-F10 cells, the number of surface lung tumours was marke dly reduced. Densitometric analyses performed on digitalized microscop ic images of histological sections of lung were used to estimate the f requency (number of lung foci; NLF) and the size (average area of meta static foci; AMF) of the resulting tumour foci. These parameters were correlated to the proliferation (AMF) and invasion (NLF) of melanoma c ells in vivo. The data showed a similar theophylline-induced decrease in the AMF and NLF values (71%, P < 0.01). Caffeine treatment produced a more pronounced decrease in the AMF (61%, P < 0.01) than in the NLF (25%, P < 0.01). To our knowledge, this is the first demonstration th at theophylline and caffeine possess the capacity to inhibit not only cell proliferation, but also the metastatic behaviour of melanoma canc er cells. (C) 1998 Lippincott-Raven Publishers.