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Interleukin‐1β induces tumor necrosis and early morphologic and metabolic changes in transplantable mouse tumors. Similarities with the anti‐tumor effects of tumor necrosis factor α or β
Author(s) -
Belardelli F.,
Proietti E.,
Ciolli V.,
Sestili P.,
Carpinelli G.,
Di Vito M.,
Ferretti A.,
Woodrow D.,
Boraschi D.,
Podo F.
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910440121
Subject(s) - tumor necrosis factor alpha , necrosis , extravasation , cytokine , biology , ratón , pathology , choline , cancer research , chemistry , endocrinology , immunology , medicine
Peri‐tumoral injection of recombinant human interleukin‐I ß in mice transplanted s.c. with Friend erythroleukemia cells (FLC) resulted in marked inhibition of tumor growth and increased survival. However, in vitro treatment of FLC (745 or 3CI‐8) with IL‐Iß barely inhibited cell multiplication. IL‐Iß, injected into established solid tumors, induced marked morphologic changes. Vascular congestion and focal extravasation of erythrocytes were observed as early as 6 hr after injection with IL‐Iß of FLC and L1210 tumors and HeJ16 fibrosarcomas. Focal areas of disaggregation of tumor cells and tumor necrosis were observed 6 and 24 hr after IL‐I injection. These morphologic changes were similar to those observed in FLC tumors or HeJ16 fibrosarcomas treated with TNF‐α or ß. These cytokines determined morphological changes in tumor blood vessels of FLC tumors within I hr of injection. Freshly dissected FLC tumors and their tissue extracts were studied by Nuclear Magnetic Resonance (NMR) spectroscopy, shortly after peri‐tumoral injection of IL‐Iß or TNF‐ß. After 6 hr, both cytokines induced a 3‐fold reduction in the levels of two catabolites, glycerophosphorylcholine and glycerophospho‐rylethanolamine, an accumulation of sn‐glycerol 3‐phosphate and a more than 10‐fold increase in the choline/phosphoryl‐choline ratio. These results are similar to those reported for TNF‐α, and can be interpreted on the basis of an activation of glycerophosphorylcholine phosphodiesterase (EC 3.1.4.2) and partial inhibition of choline kinase (EC 2.7.1.32). IL‐Iß and TNF‐ß (like TNF‐α) also induced alkaline shifts (0.10‐0.25 units) in the average intratumoral pH value. We suggest that alterations of tumor blood vessels may be the primary events in solid tumors treated with IL‐Iß or TNF. Such alterations lead to early changes in tumor metabolism and subsequent tumor cell degeneration.