CLONAL GROWTH OF COLORECTAL-CARCINOMA CELL-LINES TRANSPLANTED TO NUDE-MICE

It is generally assumed that tumor progression is a microevolutionary process in which increasingly aggressive clones, generated through gen etic instability, emerge in an initially monoclonal lesion. The presen t study was undertaken to determine how rapidly a dominant clone will emerge from an initial polyclonal situation, and whether dominance of these clones is a prerequisite for the onset of metastasis. To this en d, colon-carcinoma cells were infected in culture with an amphotropic retroviral vector containing the neomycin-phosphotransferase gene, whi ch makes cells resistant to neomycin. A heterogeneous population of ne omycin resistant cells carrying random retroviral integrations was xen ografted to the subcutis and to the cecum of nude mice. The xenografts obtained, as well as the available metastases, were analyzed as to vi ral integrations by Southern blotting. The results show that, (i) clon al selection already takes place during growth of the primary tumor; ( ii) dominant clones also generate metastases. The retroviral integrati on pattern of metastases turned out to be identical to that found in t he primary xenografts. This pattern remained unchanged in tumors obtai ned after serial transplantations of cells cultured from metastases. ( C) 1997 Wiley-Liss, Inc.