Proliferation behavior of xenografted human tumors: a flow cytometric study

The proliferation behavior of three adenocarcinomas derived from the colon rectum, colon sigmoideum and the lung was pursued by flow cytophotometry between 0 h and 38 h after heterotransplantation to athymic mice. On principle, the same pattern of alterations was observed in the case of all three tumors, the time parameters slightly varying in dependence on growth velocity. At first, the number of intact tumor cells markedly decreased during 16-24 h after transplantation, being accompanied by an increase of cellular debris and an immigration of numerous host animal cells; the latter became the quantitatively preponderant portion of cells between days 2 and 8. On day 6, the tumor cell population began to proliferate. At first, the G1 peak rose, followed by the appearance of tumor cells in the S and (G2 + M) phases. Simulataneously, the relative portions of mouse cells and cellular debris diminished. Between days 14 and 30, when maximum rates of macroscopic growth of the heterotransplants were achieved, the cytokinetic features of the xenografts had stabilized and were characterized by the presence of a small portion of mouse cells and a prominent tumor cell population, most cells being in the G1 phase and a smaller number passing through the S and (G2 + M) phases. Beyond day 30, degeneration phenomena again occurred, which were reflected by a decay of mouse and tumor cell populations and a simultaneous increase of cell fragments. By cytokinetic means, the results of the present study reveal a multistep development of human tumors after heterotransplantation into nude mice, and confirm the importance of host-supplied cells for the removal of degenerated tumor cells and the induction of tumor cell proliferation. Moreover, the results show that a stable cytokinetic pattern is found only during the phase of macroscopic tumor growth and the following phase of steady state.