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Direct and indirect effects of interferon on in vivo murine tumor cell growth
Abstract:
We cloned two sublines (S1 and R1) of murine Meth A fibrosarcoma cells with respect to their sensitivity to a murine alpha/beta-interferon (IFN) preparation. The growth of S1 cells was suppressed and that of R1 cells was hardly affected by IFN in vitro. This was also the case with cells enclosed in cell-impermeable diffusion chambers in peritoneal cavities. Nevertheless, IFN suppressed the growth of not only S1 cells but also R1 cells in mice inoculated i.p. with these cells, and the survival rates of both S1 cell recipients and R1 cell recipients were markedly improved. S1 cells were observed microscopically to be injured by the direct effect of IFN in vitro and in vivo, but R1 cells in in vitro culture with IFN and those surviving in vivo in the presence of IFN appeared to proliferate well. In the peritoneal cavity of R1 recipients treated daily with IFN, the recruitment of macrophages was enhanced in comparison with untreated R1 recipients. Adherent peritoneal exudate cells obtained from IFN-treated, R1-bearing mice were highly suppressive for the in vitro growth of not only R1 cells but also allogeneic and human cells. The role of macrophages in the indirect effect of IFN on tumor cell growth is discussed.
Insights
Murine alpha/beta-interferon (IFN) suppressed fibrosarcoma growth in vivo, improving survival rates. This effect involved direct cell injury and enhanced macrophage activity, particularly in resistant cell lines.
Area of Science:
- Immunology
- Cancer Biology
- Virology
Background:
- Murine Meth A fibrosarcoma cell lines (S1 and R1) exhibit differential sensitivity to alpha/beta-interferon (IFN).
- Understanding interferon's role in cancer therapy requires investigating its direct and indirect effects on tumor cells and the immune system.
Purpose of the Study:
- To investigate the in vitro and in vivo effects of murine alpha/beta-interferon (IFN) on two sublines of Meth A fibrosarcoma cells with differing sensitivities.
- To elucidate the mechanisms underlying IFN's anti-tumor activity, including direct cellular effects and immune cell modulation.
Main Methods:
- Cloning of S1 (sensitive) and R1 (resistant) murine fibrosarcoma sublines.
- In vitro and in vivo cell growth assays with IFN treatment.
- Analysis of cell injury and proliferation.
- Assessment of peritoneal immune cell recruitment and function in IFN-treated tumor-bearing mice.
Main Results:
- IFN directly inhibited S1 cell growth in vitro and in vivo, while R1 cell growth was less affected directly.
- IFN treatment significantly improved survival rates in mice bearing either S1 or R1 tumors.
- IFN enhanced macrophage recruitment and activity in the peritoneal cavity of R1 recipients.
- Peritoneal exudate cells from IFN-treated mice suppressed the in vitro growth of various tumor cells, indicating an indirect anti-tumor effect.
Conclusions:
- Murine alpha/beta-interferon exhibits potent anti-tumor effects against fibrosarcoma in vivo, extending beyond direct cytotoxicity to sensitive cells.
- Enhanced macrophage-mediated anti-tumor immunity plays a crucial role in IFN's therapeutic efficacy, particularly against less sensitive tumor cells.
- IFN holds promise as an immunotherapeutic agent for cancer, capable of modulating the tumor microenvironment to promote tumor rejection.