The murine Fc-gamma (Fc gamma) receptor type II B1 is a tumorigenicity-enhancing factor in polyoma-virus-transformed 3T3 cells.

The murine receptor for the Fc portion of IgG is a molecule expressed by cells of the immune system. This study suggests the hypothesis that Fc gamma receptor type II B I (Fc gamma RIIB I) functions as a progression-enhancing factor when expressed ectopically on non-lymphoid tumor cells. It has been shown previously that BALB/c 3T3 cells transformed in vitro with polyoma virus (PyV) do not express Fc gamma RII but acquire the expression of this receptor following an in vivo passage in syngeneic mice. The specific Fc gamma RII transcript present in tumor cells was identified in this report as Fc gamma RIIB I (BI). In order to determine whether or not the ectopically expressed Fc gamma RII plays a role in the progression of these transformed cells, PyV-transformed 3T3 cells were transfected with BI-cDNA. The BI transfected cells were tested for their ability to form local tumors in syngeneic mice, as compared to transfected cells which express the co-transfecting neomycine resistance (neores) DNA alone or together with the lacZ gene. Fc gamma RIIB I expressors exhibited a significantly higher tumorigenic phenotype than FcR-negative controls, though both types of cells exhibited the same growth curve in vitro. The ability of Fc gamma RIIB I to act as a potentially tumorgenicity-enhancing factor was also demonstrated as Fc gamma RII was expressed by tumor cells, originating from inoculated Fc gamma RIIB I-transfected cells, or from inoculation of a mixture of receptor-positive and -negative cells. B I-expressing cells dominated the tumor-cell population over non-expressors. This dominance strengthened the hypothesis that FcR plays a role in tumor progression in vivo.

Phenotypic properties of 3T3 cells transformed in vitro with polyoma virus and passaged once in syngeneic animals.

Cloned BALB/c 3T3 cells transformed in vitro with polyoma virus (PyV) acquired a higher tumorigenicity phenotype after a single in vivo passage. Some of the in vivo passaged cells (CTC cells) exhibited also a higher metastatic phenotype than cells from the same clones that were maintained only in culture (C cells). A phenotypic comparison between CTC and C cells was performed. It was found that most CTC lines exhibited a higher binding to laminin compared to their clonal C cell ancestors. Some CTC cells were less sensitive to the cytotoxic effects of TNF-alpha than the corresponding C cells. CTC cells originating from tumors which appeared after a long latency period (late tumors) tended to express Fc gamma RII while CTC cells originating from tumors which appeared after a short latency period (early tumors) as well as the corresponding C cells tended not to express Fc gamma RII. The expression of a membrane epitope recognized by a monoclonal antibody expressing specificity towards PyV transformed cells, was down-regulated on late tumor cells compared to early tumor cells. Transfection of cloned PyV-transformed BALB/c 3T3 cells with the beta 1Fc gamma RII gene augmented the tumorigenicity and metastatic phenotype of the transfectants compared to control transfectants.

Possibilities of interference with the immune system of tumor bearers by non-lymphoid Fc gamma RII expressing tumor cells.

The ectopic expression of Fc gamma RII by PyV transformed 3T3 cells derived from tumors of long latency has been established. It was suggested that this expression is one of several changes conferring upon the cells an increased capacity for survival. We found that in one case cells expressing a very high level of Fc gamma RII had also a very high metastatic phenotype as compared to FcR negative cells. Direct evidence that Fc gamma RIIbl functions as a progression factor was provided by transfection experiments. The transfected gene conferred an increased malignancy and invasive phenotype upon PyV or c-Ha-ras transformed cells. In the present study we tested the possibility that Fc gamma RII expressing tumor cells could interfere with the immune system. The following subjects were investigated: 1) The ability of Fc gamma R on the tumor cells to bind the ligand and/or release IBF. 2) The effect of a local accumulation of ligand and/or IBF (assumed to take place in situ in the tumor) on Fc gamma RII expressing T cells. It was found that both tumor-derived receptor positive and beta l transfected PyV transformed cells were capable of binding aggregated mouse IgG. The binding of bivalent ligand was followed by an increase in membrane Fc gamma RII expression. Also both types of cells were capable of releasing IBF. We then tested the possibility that a local accumulation of IgG within the tumor could effect Fc gamma R expressing T cells. It was found that aggregated mouse IgG (as well as IgGl) could stimulate the proliferation of the T cell hybridoma (T2D4) and other Fc gamma RII expressing T cells. We also found that the expression of beta Fc gamma RII specific mRNA peaked at the logarithmic phase of T2D4 cultures, in parallel with their maximal potential to release IBF. Several pathways for interference with the immune system are suggested.