Inherent tumorigenic and metastatic properties of rat-1 and rat-2 cells

Rat-1 and Rat-2 cells have been used in many studies of in vitro transformation and are widely assumed to be nontumorigenic because of their low incidence of focus formation, their poor growth in soft agar, and their reported failure to form tumors in animals. We examined more carefully the relationship between the in vitro and in vivo behavior of these cells and found that in spite of their in vitro characteristics, injection of these cells into Fischer rats invariably produced invasive tumors which frequently metastasized. When cells from primary tumors or metastases were cultured in vitro, the resultant cell lines were usually morphologically indistinguishable from parental cells and neither formed foci nor grew in soft agar. Thus, in vitro growth patterns do not correlate well with in vivo behavior in these cells and their inherent tumorigenicity warrants caution in the interpretation of results of in vitro transformation studies.