DUAL ROLE OF FIBROBLASTS IN TUMOR-CELL GROWTH

Vast experience with cultivating biopsies from human tumors indicates that in most cases the admixture of fibroblasts has a negative effect on growth of tumor cells, Only rarely is observed help provided by til e fibroblasts. It has also long been known that fibroblasts can inhibi t by contact themselves and also produce growth factor(s) promoting ce ll proliferation. We have used three permanent squamous cell carcinoma lines and fibroblasts derived from biopsies of trachea to study this paradox. The inhibitory activity of fibroblasts is contact-dependent i n a cell membrane-bound factor, which is trypsin sensitive, We prepare d microsomal fractions (MF) from aged (more than 40 passages) fibrobla sts and followed their effect on proliferation of the tumor cells in a n MTT assay, MF from all three fibroblast lines inhibited the tumor ce lls. Most regularly was this phenomenon observed with line UM-SCC 22B. Not all tumor cells are immortal. On the contrary, a large portion of them undergoes terminal differentiation. With the line UM-SCC 22B we tested the possibility that MF from fibroblasts call increase the port ion of tumor cells which will senescence after few mitoses, The immort al cells were defined as cells capable in 8 or 13 days of forming colo nies of more than 50 or 200 cells, The senescent cells were defined as cells not capable of producing within the same period of time colonie s of more than 12 or 30 cells, The MF was able to increase the number of small colonies, i.e. the number of senescent tumor cells. The fibro blasts of the same passage level were releasing soluble growth factor( s) promoting growth of cells. Fibroblasts can apparently simultaneousl y inhibit growth by contact and release factor(s) promoting growth of cells. The final outcome is a result of the balance between these two forces. This balance is regulated by many intrinsic and extrinsic forc es.