Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Prostatic cancer commonly causes osteoblastic bone metastases.
• These metastases show increased osteoblasts but not marrow fibrosis.
• A paracrine mechanism involving selective osteoblast stimulation is hypothesized.

Purpose of the Study:

• To test if prostatic cancer cells produce factors selectively stimulating human osteoblasts.
• To investigate the mitogenic activity of the human prostatic tumor cell line, PC3.
• To characterize the nature of this osteoblast-specific mitogenic activity.

Main Methods:

• PC3 cell-conditioned medium (CM) was used to treat human osteoblasts and fibroblasts.
• Proliferation was assessed by [3H]thymidine incorporation and cell counting.
• Specific assays were performed for known bone growth factors (IGF I, IGF II, bFGF, TGF-β).
• Biochemical characterization included heparin binding, acid/dithiothreitol resistance, and chromatography (Sephadex G-75, Mono S FPLC).

Main Results:

• PC3 CM significantly stimulated human osteoblast proliferation (200-950%) but not human fibroblast proliferation.
• PC3 CM increased osteoblast cell numbers, but not fibroblast cell numbers.
• Known bone growth factors in PC3 CM could not account for the observed mitogenic activity.
• PC3 CM showed additive effects with known bone mitogens, indicating an independent mechanism.
• The PC3-derived mitogen is a Mr 26,000-30,000 basic protein, heparin-unbound, and resistant to acid and dithiothreitol.

Conclusions:

• PC3 cells release a novel mitogen with high specificity for human osteoblasts over human fibroblasts.
• This mitogen is distinct from previously identified bone growth factors.
• The production of this osteoblast-specific mitogen by prostatic carcinoma cells may contribute to osteoblastic bone metastases.