Artificial tumor: a novel heterotypic, polymorphic, three-dimensional in vitro model of individual human solid tumors

We established a new complex three-dimensional in vitro model called artificial tumor (ArT), which stimulates individual human solid tumors. In contrast to the generally used spheroid models consisting of tumor cells only, the model described in the present report is composed of both tumor cells and tumor stromal cells. We created ArTs as a replica of colon carcinomas, composed of colon carcinoma cells, colon fibroblasts, and as supportive skeleton fibrous tissue from human colon. All cellular components were established from the same surgically obtained colon carcinoma specimen. The ArTs studied came from 4 types of colon carcinomas; mucinous, well, moderately and undifferentiated colon carcinomas. Among all types of colon carcinomas ArTs could be established with a high rate of success, i.e. 81%. Cells growing for 5 days on the fibrous tissue under normal culture conditions formed tumors up to 2,000 microns in diameter. Morphological studies showed that tumor cells grown as ArTs maintained the individual characteristics of the original tumor; for example, a comparable heterogeneity in CEA expression and/or maintenance of the differentiation stage. Polarized tumor cells were linked with the tumor stroma-simulating structure by their basal cell membrane, and formed central lumina lined by the apical membranes of the tumor cells, a structure quite similar to the tissue architecture of colon carcinomas in vivo.