GROWTH AND CHEMOTHERAPEUTIC RESPONSE OF CELLS IN A HOLLOW-FIBER IN-VITRO SOLID TUMOR-MODEL

Background: Cancer treatments that appear promising in tissue culture are often less effective in solid tumors, in part because of the proli ferative and microenvironmental heterogeneity that develops in these t umors as they grow. Heterogeneous tumor models are thus needed for dru g screening. Purpose: Our goal was to develop and test for drug evalua tion a solid tumor model based on cell growth inside biocompatible hol low fibers. Methods: Building on the experience of Hollingshead and co -workers with a sparse-cell, hollow-fiber tumor model, we tested six h uman tumor cell lines for in vitro growth inside 450-mu m internal-dia meter polyvinylidine fluoride fibers and examined them histologically. Human SW620 colon carcinoma cells grown in hollow fibers were also ex amined using electron microscopy, and their doxorubicin sensitivity wa s assessed. A colorimetric assay based on sulforhodamine B was adopted to replace the more cumbersome clonogenic cell survival assay. Result s: Five of the human tumor cell lines tested grew to confluence, formi ng heterogeneous in vitro tumors with subpopulations of viable and nec rotic cells. For SW620 hollow-fiber tumors, maximum viable cell popula tions in excess of 10(8) cells/ml were obtained after 8 days of growth . This viable cell density remained roughly constant for 3-4 days, per mitting dose-response experiments over this time interval. Tumor cells in hollow fibers were much more resistant to a 4-hour doxorubicin exp osure than were tumor cells in monolayers: LC(50) values (i.e., the dr ug concentrations at which the plating efficiency equals one-half the plating efficiency of untreated cells) of 3.5 mu M and 0.16 mu M were obtained for hollow-fiber tumors and monolayers, respectively. LC(50) values decreased when drug exposure time was increased. Results from t he colorimetric assay were in agreement with those from the clonogenic assay. Conclusion: The successful growth of tumor cells to confluence in hollow fibers and the feasibility of performing in vitro drug dose -response experiments with a relatively easy colorimetric assay demons trate the potential of the hollow-fiber solid tumor model as a tool fo r experimental therapeutic research. Implication: Hollow-fiber solid t umors may prove useful for experimental drug evaluation.