Expression and function of colony-stimulating factors and their receptors in human prostate carcinoma cell lines

The predeliction for prostate carcinoma cells to metastasize to bone suggests the hypothesis that bone and/or bone marrow-derived factors may promote prostate carcinoma cell growth or survival, or serve as chemoattractants for these cells.

We screened three prostate carcinoma cell lines, DU-145, PC-3, and LNCaP, for the expression of several hematopoiesis-associated colony-stimulating factors (CSFs) and their receptors using RT-PCR (reverse transcriptase-polymerase chain reaction) and immunohistochemical methods, and examined their functional effects.

All of these cell lines express granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), and the DU-145 and PC-3 lines express stem-cell factor (SCF), as determined by RT-PCR and ELISA. Each of these cell lines expresses the receptors for SCF, GM-CSF, M-CSF, and granulocyte colony-stimulating factor (G-CSF). M-CSF enhanced the soft-agar clonogenicity of PC-3 and DU-145 cells, and GM-CSF stimulated all three cell lines. SCF stimulated the clonogenic growth of DU-145 cells. G-CSF marginally abrogated the induction of cell death in the PC-3 and LNCaP cell lines under serum-free conditions. GM-CSF and M-CSF stimulated modest chemotaxis of PC-3, DU-145, and LNCaP cells (most prominently in PC-3 cells).

These data suggest that 1) CSFs may be part of a network of paracrine and autocrine loops that modulate prostate carcinoma cell activity, and 2) the growth-stimulatory, survival-enhancing, and/or chemotactic actions of bone marrow-derived CSFs on prostate carcinoma cells may explain in part why bone is a preferential site of prostatic carcinoma metastases.