COMPARATIVE IN-VIVO AND IN-VITRO PROLIFERATION OF MURINE TUMOR-CELLS IN THE BONE MICROENVIRONMENT

To examine the effect of bone microenvironmental factors on the growth of metastatic cells, the in vivo proliferative features of three muri ne cell lines were determined at skeletal metastatic sites and correla ted with their ability to grow in vitro in the presence of bone-derive d factors. Bones, ovaries, adrenals and the brain were most affected b y metastasis, following an intraarterial injection of B16/F1 and B16/F 10 melanoma and FS/L10 fibrosarcoma cells into C57BL/6 mice. Melanoma cells showed a marked metastatic preference for bone, while fibrosarco ma cells developed brain metastasis in all animals. Tumor burden in bo nes was highest (19+/-2%) for B16/F10 cells, compared to B16/F1 (10+/- 2%) or FS/L10 (3+/-1%) cells. Autoradiographic studies demonstrated or gan- and cell type-specific differences in tumor cell proliferation, w ith B16/F10 cells displaying the lowest labelling indexes in bone (12/-2% for B16/F10 vs 28+/-2% and 27+/-4% for B16/F1 and FS/L10 cells, r espectively). To test if bone-derived factors differentially affected tumor cell growth in these three cell lines H-3-thymidine uptake by th ese tumor cells was assessed after in vitro incubation with bone-deriv ed conditioned medium. Under these conditions, we observed stimulation of B16/F10 cell proliferation, but inhibition of uptake in the other two cell lines. Thus, these results demonstrate that, in this in vivo experimental model, growth properties of metastatic cells are organ- a nd cell type-specific. Additionally, we show that the in vitro prolife rative behavior of tumor cells in the presence of bone-derived factors correlates and may predict skeletal tumor growth properties in vivo.