Interferon-mediated enhancement of metastasis. Are MHC antigens involved?

Abstract

The relationship between major histocompatibility complex (MHC) antigens and metastasis was investigated on B16 melanoma variants. B16 cell lines express low amounts of murine MHC (H-2) antigens. A high expression can be induced in line B16-A by in vitro treatment with immune interferon (IFN-gamma) or by in vivo transplant in allogeneic mice. The increase of H-2 antigens correlated with an enhancement of lung colonization in young syngeneic mice. The higher metastatic capacity of B16-A cells with induced high levels of H-2 antigens was observed also in adult mice and in young mice pretreated with cyclophosphamide. These results were confirmed investigating the behaviour of a mutant B16 clone (B78H1) which was selectively resistant to the H-2-inducing action of IFN-gamma: lung colonization ability was not increased by IFN pretreatment. The study of variants derived from individual B16-A lung colonies revealed a wide range of H-2 levels. Variants with a low expression had a low colonization ability; one out of two variants with a high H-2 expression also was poorly colonizing. IFN-gamma-mediated H-2 expression appeared to act as an enhancer, rather than a determinant of B16 metastatic capacity.

Equus caballus Major Histocompatibility Complex Class I Is an Entry Receptor for Equine Herpesvirus Type 1

“…B78H1 murine melanoma cells that are highly resistant to EHV-1 were rendered completely susceptible to EHV-1 infection after expression of the cDNA encoding equine MHC-I. The inability of EHV-1 to infect parental B78H1 cells is most likely explained by the lack of MHC-I receptor expression on these cells (8,33). Likewise, the ability of EHV-1 to infect a diverse array of cells obtained from different species (42) may be explained by the ubiquitous expression of MHC-I receptors on nearly all nucleated cells (5,25) and the structural homology exhibited between MHC-I molecules of different species (25).…”

IFN‐α1 gene transfection completely abolishes the tumorigenicity of murine B16 melanoma cells in allogeneic DBA/2 mice and decreases their tumorigenicity in syngeneic C57BL/6 mice

“…the immune response being directed against both viral gp70 glycoproteins and a surface tumor antigen (Sala et al, 1992), and we showed that IFN-a transfection of these cells induced a highly effective, long-lasting tumorspecific immunity (Ferrantini et al, 1993). We wanted to know whether the tumorigenicity of a non-immunogenic tumor, such as the murine B16 melanoma (Lollini et al, 1985(Lollini et al, , 1987, could also be decreased by IFN-aI gene expression. After continued passage in vitro, this tumor does not express class-I molecules (Nanni et al, 1993;Lollini et al, 1985), does not confer protection upon animals immunized with irradiated cells (Dranoff et a/., 1993), and grows in and kills allogeneic mice (Nanni et al, 1983;Lollini et al, 1985Lollini et al, , 1987.…”

Recombinant interferon alpha and gamma modulate the invasive potential of human melanoma in vitro

“…The metastatic potential of cancer cells was increased also in vivo by using pre-treatments with gamma IFN (Ramani and Balkwill, 1987;Lollini et al, 1987). The enhanced metastasis also correlated to an increase in major histocompatibility complex (MHC) expression (Lollini et al, 1987). Taken together, these data suggest that the enhanced metastatic potential of interferon-treated cells may be related to antigen-inducing effects of interferon in vivo and may also be due to a short exposure of the cancer cells to the drugs.…”

“…Also in agreement with our findings is an investigation by Siegal et al (1982) who showed a considerable enhancement of the invasiveness in vitro of Ewing sarcoma cells treated with IFN alpha and beta. The metastatic potential of cancer cells was increased also in vivo by using pre-treatments with gamma IFN (Ramani and Balkwill, 1987;Lollini et al, 1987). The enhanced metastasis also correlated to an increase in major histocompatibility complex (MHC) expression (Lollini et al, 1987).…”