Heterogeneity in Growth Pattern and Drug Sensitivity of Primary Tumor and Metastases in the Human Tumor Colony-forming Assay¹

The human tumor colony-forming assay was used to compare primary tumors with their metastases. Cell suspensions were prepared from 38 primary tumors and from metastases taken simultaneously from the same patient. Considerable differences were observed. Cloning efficiency was significantly higher in the cell suspensions taken from metastases than from material from the primary tumor. In 10 paired samples which allowed in vitro drug sensitivity testing, the data showed no satisfactory correlation in resistance or sensitivity to cytostatic drugs between primary tumor and metastases. The regression coefficient calculated for the different cytostatic agents (Adriamycin, bis(chloro)ethylnitrosourea, 5-fluorouracil, 4-hydroxy-peroxycyclophosphamide) varied between 0.02 and 0.1. The results indicate that experiments designed to analyze chemosensitivity of tumor cells in the tumor colony-forming assay should be interpreted with caution. In particular, in vitro sensitivity data obtained from the primary tumor may have severe limitations in planning treatment of metastatic disease.