Modulation of growth of a human prostatic cancer cell line (PC-3) in agar culture by normal human lung fibroblasts.

The influence of normal human lung fibroblasts (NLF) on the clonal growth of human prostatic carcinoma cells (PC-3) in soft agar was studied. PC-3 growth was assessed by both colony-forming efficiency and clonal growth rate as estimated from increase in colony diameter. Effects of anchored NLF (proliferating cell monolayer) and nonanchored NLF (nonproliferating cells embedded in agar) on PC-3 growth were compared. Marked differences were observed. Anchored NLF inhibited whereas nonanchored NLF stimulated PC-3. Under suboptimal growth conditions (7% fetal bovine serum), PC-3 growth was stimulated about three-fold when NLF was added to the agar at a NLF:PC-3 seeding ratio of 60:1. Similar seeding ratios using anchored NLF cells caused a 98% inhibition of PC-3 growth. Control experiments with NLF-seeded coverslips on agar cultures ruled out medium depletion as a cause of the PC-3 inhibition. PC-3 inhibition was independent of NLF cell contact, required the continued presence of NLF cells, and was thus attributed to a diffusible, labile factor derived from anchored NLF monolayers. Kinetic analysis was used to determine the nature of the nonanchored NLF-fetal bovine serum interaction on stimulated PC-3 growth. Although the NLF factor was not a component of fetal bovine serum, it acted synergistically with it to stimulate PC-3 growth. It was concluded that there were strong correlations between (a) nonanchored NLF cells and PC-3 stimulation and (b) anchored NLF cells and PC-3 inhibition.