| Title: |
Mechanisms of experimental cancer cachexia. Interaction between mononuclear phagocytes and colon-26 carcinoma and its relevance to IL-6-mediated cancer cachexia |
| Authors: |
Strassmann, G; Jacob, C O; Evans, R; Beall, D; Fong, M |
| Source: |
The Journal of Immunology ; volume 148, issue 11, page 3674-3678 ; ISSN 1550-6606 0022-1767 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
1992 |
| Description: |
In a recent report we showed that IL-6 is an important mediator of experimental cancer cachexia in the colon-26 (C-26) tumor system. In culture, on a per cell basis, C-26.IVX cell line (which develops tumors and induces severe cachexia of syngeneic hosts) produces up to 60-fold less IL-6 than single cell suspensions prepared from freshly excised tumors. In this study, the mechanism behind this observation was investigated. Analysis of the cellular composition of progressing C-26 tumors indicated they contained up to 6% of macrophages. T cells, B cells, and granulocytes were not detected in the tumors. Because C-26.IVX line grown in vitro contained no macrophages, the possibility that macrophage products may augment IL-6 synthesis by the tumor cells was tested. Indeed, IL-1 beta in a dose-dependent manner and at picogram amounts could potentiate IL-6 production by the C-26 cell line. The presence of high affinity receptors for IL-1 on the C-26.IVX cell line was established. These cells expressed approximately 1500 IL-1 sites per cell with a dissociation constant of approximately 20 pM. Next, we attempted to mimic the situation in vivo by coculture of C-26.IVX cells with syngeneic peritoneal macrophages and found that this condition gives rise to an augmented IL-6 production similar to that observed with in vivo derived tumor cells or rIL-1 beta-treated C-26.IVX cells. Furthermore, anti-IL-1 type I receptor antibody completely blocked C-26.IVX IL-6 production induced by either rIL-1 beta or by peritoneal macrophages. Taken together, these data suggest a pathway of IL-6 production by C-26 tumors that involves a cellular interaction between IL-1R-expressing tumor cells and host-derived macrophages. The results also suggest that this interaction significantly contributes to cachectic events endured by the tumor-bearing host. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.148.11.3674 |
| Availability: |
https://doi.org/10.4049/jimmunol.148.11.3674; https://academic.oup.com/jimmunol/article-pdf/148/11/3674/62379126/1534101.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.5EB095FA |
| Database: |
BASE |