Expression of c-kit and kit-ligand in benign and malignant prostatic tissues

The tyrosine kinase receptor c-kit and its ligand [kit ligand (KL) or stem cell factor (SCP)] exert a broad range of biological activities during orga nogenesis and normal cell development. Recent studies have revealed that al tered c-kit levels occur in a variety of malignancies and cancer cell lines . KL has also been shown to stimulate the growth of malignant cells, as wel l as to promote chemotaxis. We had previously reported expression of KL in stroma cells of normal human prostate. The present study was undertaken in order to analyze the patterns of expres sion of c-kit and KL in a well characterized set of prostatic tissues, Incl uding normal prostate (n=4), benign prostatic hyperplasia (BPH) (n=53) and adenocarcinoma (n=46) samples. The distribution of c-kit and KL proteins wa s studied by immunohistochemical analyses, while transcript levels were det ermined by in situ hybridization with specific RNA probes on a subset of th e benign and malignant tissues referred above. In addition, reverse-transcr iptase polymerase chain reaction (RT-PCR) was performed to determine levels of c-kit and KL,expression in cultures of epithelial and stroma cells, as well as in the prostate cancer cell lines LNCaP, DU145 and PC3. c-kit protein in normal prostate was exclusively detected in mast cells by immunohistochemistry and in situ hybridization. However, c-kit transcripts, but not c-kit protein, were detected in low levels and with an heterogeneo us pattern in basal epithelial cells of ducts and acini. c-kit in BPH was d etected in epithelial cells in 9 of 53 (17%) specimens, c-kit protein expre ssion in malignant epithelial cells was identified in 1 of 46 (2%) tumors. However, c-kit transcripts were detected in low levels by in situ hybridiza tion in most of the tumors analyzed. KL protein and transcripts in normal prostate were detected in high levels in stroma cells. However, epithelial cells were unreactive for anti-KL anti body, but showed low levels of KL transcripts mainly in cells of the basal layer. Basal epithelial cells in hyperplastic glands showed KL expression i n 13 of 53 (24%) specimens. KL protein in tumor cells was noted in 18 of 46 (39%) cases. c-kit transcripts were not found in normal prostate and in the 3 cancer cel l lines analyzed by RT-PCR, however,:it was present in cultured epithelial cells of BPH, and in cultures of stroma cells from both normal and BPH. The majority of cultured cell lines of epithelial and stromal origin displayed considerable levels of KL. In addition all prostate cell lines studied sho wed significant levels of KL transcripts. In summary, co-expression of c-kit and KL in a subset of BPH cases may sugg est an autocrine mode of signaling. Data from this study reveals that alter ed patterns of c-kit and KL expression are associated with BPH and adenocar cinoma of prostate. It appears that KL induces mast cells proliferation and maturation and enhances their release of protease. This could explain the accumulation of mast cells at tumor sites, a phenomenon that was not observ ed in normal prostate or BPH samples.