Generation of invasive and metastatic variants of a non-metastatic T-cell lymphoma by in vivo fusion with normal host cells

Abstract

Intravenous inoculation of the AKR mouse-strain-derived BW lymphoma into CBA recipients resulted in a case of liver metastasis; cells derived from this metastatic nodule were termed BW-Li cells. BW-Li cells, upon reinoculation, generated metastases in the spleen, liver, kidney and ovaries in 100% of CBA recipients. Furthermore, BW-Li cells, in contrast to BW cells, were found to infiltrate in vitro monolayers of hepatocytes, thus confirming their inherent invasive potential. Analysis of the alloantigenic phenotype of BW-Li cells revealed that such cells were Thy 1.1+, Thy 1.2+, Lyt 1.2+, Lyt 1.1-, Lyt 2- and H-2Dk+, as compared to BW cells which exhibited the membrane phenotype Thy 1.1+, Thy 1.2-, Lyt 1.2-, Lyt 1.1-, Lyt 2-, H-2Dk-. BW-Li cells also differed functionally from BW cells since these cells secreted IL-2 upon stimulation with Concanavalin A. BW tumor transplantation experiments were repeated in a semi-allogeneic F1 strain combination, i.e. (AKR X CBA)F1, and again a case of massive liver metastasis was observed. Cells derived from these liver metastases (termed BW-O-Li) manifested an invasive and metastatic potential similar to that of BW-Li cells. Furthermore, BW-O-Li cells secreted IL-2 upon stimulation with Con A and manifested the following alloantigenic phenotype: Thy 1.1+, Thy 1.2+, Lyt 1.2+, Lyt 1.1-, Lyt 2-, H-2Dk+ and H-2Kk+. These results indicate that BW-Li and BW-O-Li cells are functional T-cell hybrids which express T-cell markers derived from BW cells and Thy 1.2+ CBA host cells. The acquisition of host-derived T-cell properties may have led to the expression of metastatic and invasive capabilities. From these results we conclude that the acquisition of metastatic properties following somatic cell fusion with normal lymphoreticular cells may represent a mechanism for tumor progression in vivo.