Loss of malignancy during serial passage of human carcinoma in culture and discordance between malignancy and transformation parameters
Ossowski, L.; Reich, E.
Cancer Research 40(7): 2310-2315
1980
ISSN/ISBN: 0008-5472 PMID: 6992983 Document Number: 165616
Human epidermoid carcinoma (HEp-3) was adapted to growth in culture. Upon serial passage in vitro, metastatic potential and tumorigenicity progressively declined. Metastatic potential was completely lost within 2-10 wk in culture (4-14 passages); tumorigenicity declined rapidly within 50 passages, as reflected in the progressively larger inoculum required for development of detectable tumors. Beyond this time, macroscopically visible tumors were not observed during the standard 7-day growth period even with an inoculum of 107 cells. Identical results were obtained with 6 tumors adapted to grow in vitro. Metastatic potential could be recovered from cell populations retaining some tumorigenicity. This required at least 2 sequential passages on the chorioallantoic membrane. Loss of metastatic ability and tumorigenicity was accompanied by change in hormone responsiveness and by improved growth efficiency in culture as manifested by shortened doubling time and increased saturation density. Further, anchorage independence and serum independence, 2 properties that are generally correlated with the transformed phenotype, were inversely correlated with malignancy. Malignant and nontumorigenic cells were compared with respect to production of plasminogen activator, an enzyme associated with malignancy and transformation. Malignant cells produced larger amounts of plasminogen activator and enzyme production was resistant to modulation by several hormonal and nonhormonal effectors; in contrast, plasminogen activator synthesis in nontumorigenic cells was stimulated by cholera toxin and inhibited by glucocorticoids.