Production of cachexia mediators by Walker 256 cells from ascitic tumors

Abstract

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.

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

“…Our findings are surprising given the strong association between the acute phase response and reduced hepatic fatty acid oxidation. 60 Although it is possible that the acute phase response was not as robust in our study of early cachexia, differences in cytokine production (thus, the acute phase response) between the colon-26 and Walker 256 cachexia models 61,62 may better explain these disparate findings. In summary, in the present study we found PKA-induced lipolysis is enhanced in early cancer cachexia which coincided with elevated total energy expenditure and increased expression of markers of BAT thermogenesis when food intake is considered and the hepatic acute phase response.…”

Oxidative and proteolytic profiles of the right and left heart in a model of cancer-induced cardiac cachexia

“…After 7 days of growth, the ascitic tumour was harvested from the peritoneal cavity and suspended in PBS, pH 7.4. The cells were separated from the ascitic fluid by centrifugation at 570 × g for 15 min at 4 • C; the cell pellet (tumour cells plus erythrocytes) was then washed once with the same PBS solution [22]. The volume of cell suspensions was adjusted to 500 L and cell viability was evaluated by the Trypan Blue exclusion test, considering only tumour cells presenting on the Neubauer chamber.…”

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

“…[9] These pro-inflammatory circulating factors are known to play a key role in the onset of cachexia-related inflammation [9,10] and to contribute to and trigger both increased muscle breakdown and decreased muscle protein synthesis in CACS patients. [11][12][13][14][15][16] IL-1b, IL-6, and TNFa are produced by tumor cells both in animal models of cachexia [17] and in cancer patients with CACS. [18] In cancer patients, the production of pro-inflammatory cytokines -an expression of systemic inflammation -may lead to an acute-phase response [19] characterized by an increase in acute-phase proteins [20] and by decreased synthesis of albumin, pre-albumin, and transferrin.…”