Multicellular tumor spheroids of human colon carcinoma origin. Kinetic analysis of infiltration and in situ destruction in a xenogeneic (murine) host.

The relationship between destruction and concomitant host cell infiltration of human tumor xenografts has been quantitatively investigated by using the multicellular tumor spheroid model. Multicellular tumor spheroids of HT-29 human colon carcinoma cells were grown in vitro and subsequently implanted in the peritoneal cavity of BALB/c mice. At various times thereafter, spheroids were recovered and dissociated and their viability was quantitatively assessed by using a clonogenic assay. Little damage to spheroids was observed during the initial 4 days after implantation, but essentially complete destruction (greater than 99% reduction in clonogenic tumor cells) occurred between days 4 and 7. In parallel studies, host cell infiltration was assessed by light and electron microscopy both in situ on sections and on dissociated suspensions of spheroid cells. The data demonstrate the value of utilizing a model system in which both functional and morphological techniques can be combined in a quantitative assessment of the relationship between host cell infiltration and graft destruction in situ.