Production of cachexia mediators by Walker 256 cells from ascitic tumors.
In neoplasic cachexia, chemical mediators seem to act as initiators or perpetuators of this process. Walker 256 cells, whose metabolic properties have so far been little studied with respect to cancer cachexia, are used as a model for the study of this syndrome. The main objective of this research was to pinpoint the substances secreted by these cells that may contribute to the progression of the cachectic state. Since inflammatory mediators seem to be involved in the manifestation of this syndrome, the in vitro production of nitric oxide (NO), cytokines (tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)), and prostaglandin E2 (PGE2) was evaluated in Walker 256 cells isolated from ascitic tumors. After 4 or 5 h, a significant increase in NO production was observed (2.55 +/- 1.56 and 4.05 +/- 1.99 nmol NO per 10(7) cells, respectively). When isolated from a 6-day-old tumor, a significantly lower production of IL-6 and higher production of TNF-alpha than in cells from a 4-day-old tumor were observed, indicating a relationship between the production of cytokines and the time of tumor development after implantation. Considerable production of PGE(2) by Walker 256 cells isolated from the 6-day-old tumor was also observed. Polyamines were also determined in Walker 256 cells. Levels of putrescine, spermidine, and spermine did not show significant differences in tumors developed during 4 or 6 days. Direct evidence of the release of proinflammatory cytokines and PGE2 by Walker 256 cells suggests that these mediators can drive the cachectic syndrome in the host, the effect being dependent on tumor development time.
Rebeca
Rosilene
R
Department of Biochemistry, UFPR-Federal University of Paraná, Curitiba, CEP, PR, Brazil.
Bracht
Lívia
L
Noleto
Guilhermina Rodrigues
GR
Martinez
Glaucia Regina
GR
Cadena
Silvia Maria Suter Correia
SM
Carnieri
Eva Gunilla Skare
EG
Rocha
Maria Eliane Merlin
ME
de Oliveira
Maria Benigna Martinelli
MB
D000818:Animals; D001119:Arginase / Q000378:metabolism; D001202:Ascitic Fluid / Q000473:pathology*; D015317:Biogenic Polyamines / Q000378:metabolism; D002100:Cachexia / Q000209:etiology / Q000378:metabolism*; D002279:Carcinoma 256, Walker / Q000150:complications* / Q000473:pathology; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014508:Urea / Q000378:metabolism
D015317:Biogenic Polyamines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D014508:Urea; D001119:Arginase; D015232:Dinoprostone