ACCUMULATION IN NORMAL LUNGS OF LIVE TUMORIGENIC CELLS DURING SUB-CUTANEOUS GROWTH OF WEAKLY AND HIGHLY METASTASIZING TUMORS AND THEIR IN-VITRO SENSITIVITY TO GROWTH-REGULATION BY NORMAL FIBROBLASTS

The main purposes of the study were: (1) in vivo comparison of accumulation of live tumorigenic cells (LTC) in macroscopically normal lungs of animals bearing 6 s.c. Syrian hamster sarcomas differing in spontaneous metastasizing activity (SMA); (2) in vitro examination of the sensitivity of these cell strains to the growth-regulating signals of normal fibroblasts. Cell strains used differed in SMA from very weak (WM) to extremely high (HM). The numbers of LTC doses in ''normal'' lung tissue of tumor-bearing animals were determined in s.c. transplantation tests by titrating single-cell suspensions prepared from the lung tissues of 5 tumor-bearing animals, for each cell strain, every 5 days during 30 days of s.c. tumor growth, until the appearance of the first spontaneous lung metastases. The sensitivity of WM and HM cells to growth-regulating signals of normal hamster embryo fibroblasts (HEFs) was examined by in vitro co-culturing during 6 days with daily determination of H-3-TdR incorporation in the WM and HM cells grown with or without contact with HEFs. The data presented demonstrate (1) the surprisingly similar efficiency in the occupation of macroscopically normal lung tissues by live tumorigenic cells of WM and HM strains, disseminating spontaneously from the s.c. tumors; (2) the significantly lower sensitivity of HM cells, in contrast to WM, to growth inhibition by contact with HEFs and especially their marked ability to usurp the growth-stimulating signals of normal HEFs. (C) 1994 Wiley-Liss, Inc.