Prolongation of fibroblast life span associated with epithelial rat tumor development.

We have examined the proliferative behavior in culture of stromal cells of fibroblast morphology taken from various stages in the development of experimentally induced epithelial tumors in the rat thyroid. In this model long-term stimulation by an elevated level of serum thyroid stimulating hormone leads first to hyperplasia, then to multiple benign, and finally malignant tumors. Fibroblasts from hyperplastic glands, despite having already undergone more divisions in vivo, consistently showed a longer life span than normal fibroblasts in culture, averaging 16 compared with six divisions before senescing. In the three tumor bearing glands studied, all cultures have undergone more than 40 divisions (in one case over 70) and none has yet shown signs of senescence. We conclude that the life span of thyroid fibroblasts observed in culture has been reset to a higher limit by growth stimulation in vivo and furthermore that this limit may be lost altogether in fibroblasts associated with epithelial tumors.