THE MULTICELLULAR SPHEROID AS A MODEL TUMOR ALLOGRAFT

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Abstract
Multicellular spheroids of murine EMT6 mammary tumor cells were implanted into the peritoneal cavity of normal, alloimmune or athymic (nude) mice. The kinetics of spheroid damage was monitored using a clonogenic assay on dissociated preparations of the recovered spheroids. In alloimmune mice a 99% reduction in clonogenic cells was observed within 48 h, whereas in a normal allogeneic host, spheroid destruction occurred between day 4-7 after implantation. In athymic mice no reduction in tumor cell survival was detected after 14 days. Concomitantly, the composition of the host infiltrate was quantitatively assessed in situ (on fixed sections) and on dissociated preparations. Within 6 h after implantation in alloimmune mice, the spheroids were preferentially infiltrated by large numbers of neutrophils and monocytic cells. A few lymphocytes were also present. In the nonimmune host, peak infiltration was delayed for 2-3 days (6-10 days for lymphocytes). In the athymic host significant infiltration was also observed, although no spheroid destruction was detectable. Ultrastructural studies showed that several cell types were capable of forming close tumor cell contacts. The value of combining functional, morphological and topographical techniques in an assessment of the relationship between the host cell infiltrate and graft survival is discussed.