Stem cell factor (SCF): Identification of a new marker of cell proliferation in benign prostatic hyperplasia

Reiner Simak, Ursula Stix, Georg Steiner, Carlos Cordon-Cardo

Research output: Contribution to journalArticlepeer-review

Abstract

The tyrosine protein kinase receptor c-kit and its ligand SCF exert a broad range of biological activities in organogenesis and normal cell growth, and altered levels of these proteins occur in various proliferative processes. Since we have recently detected considerable expression of SCF in normal prostate tissues, we further analyzed possible alterations of SCF and c-kit in benign prostatic hyperplasia and cell lines in order to evaluate the functional significance of these molecules within the prostatic microenvironment. Using immunohistochemistry (IHC) on frozen sections of normal prostate and BPH from 105 patients, we characterized the distribution of SCF and c-kit within the stroma and epithelial compartments. In addition, levels of SCF and c-kit mRNA were assessed by RT-PCR in cultures of epithelial and stroma! cells. Proliferation assays were conducted upon stimulation of cell cultures with supernatantsand purified SCF. In normal prostate, expression of SCF was restricted to stroma cells, while epithelial cells remained unreactive; c-ktt in these tissues was exclusively found in mast cells by IHC, although cultures of stroma cells from normal glands had c-kit transcripts. In BPH, epithelial cells with de novo SCF expression were seen in 30% and with c-kit expression in 18% of the specimens. Accordingly, 4 of 7 epithelial cell cultures from BPH displayed c-k mRNA. Epithelial stimulation with recombinant human SCF and stroma supernatants demonstrated significantly increased cell proliferation rates. This effect could be abolished after preincubation with anti-c-kit antibody. In contrast to normal prostate, increased epithelial cell proliferation in BPH demonstrate abundant SCF and c-kit expression, suggesting de novo paracrine pathways of signal transduction between SCF positive stroma cells and c-kit positive epithelial cells. Coexpression of SCF and c-krt in BPH further indicates the presence of active autocrine loops, and thus the possibility of stroma-independent glandular proliferation.

Original languageEnglish
Pages (from-to)204
Number of pages1
JournalBritish Journal of Urology
Volume80
Issue numberSUPPL. 2
StatePublished - 1997
Externally publishedYes

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