C-Kit and Its Ligand Stem Cell Factor: Potential Contribution to Prostate Cancer Bone Metastasis |
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| Authors: | Christoph Wiesner Sanaa M Nabha Emanuel Burck Dos Santos Hamilto Yamamoto Hong Meng Sebastian W Melchior Fernando Bittinger Joachim W Thüroff Robert L Vessella Michael L Cher R Daniel Bonfil |
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| Affiliation: | *Department of Urology, Wayne State University School of Medicine, Detroit, MI, USA;†Department of Urology and Pathology, Johannes Gutenberg University, School of Medicine, Mainz, Germany;‡Department of Urology, University of Washington, Seattle, WA, USA;§Department of Pathology, Wayne State University School of Medicine and The Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA |
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| Abstract: | The tyrosine kinase receptor c-kit and its ligand stem cell factor (SCF) have not been explored in prostate cancer (PC) bone metastasis. Herein, we found that three human PC cell lines and bone marrow stromal cells express a membrane-bound SCF isoform and release a soluble SCF. Bone marrow stromal cells revealed strong expression of c-kit, whereas PC cells showed very low levels of the receptor or did not express it all. Using an experimental model of PC bone metastasis, we found that intraosseous bone tumors formed by otherwise c-kit-negative PC3 cells strongly expressed c-kit, as demonstrated using immunohistochemical and Western blot analyses. Subcutaneous PC3 tumors were, however, c-kit-negative. Both bone and subcutaneous PC3 tumors were positive for SCF. Immunohistochemical analysis of human specimens revealed that the expression frequency of c-kit in epithelial cells was of 5% in benign prostatic hyperplasia, 14% in primary PC, and 40% in PC bone metastases, suggesting an overall trend of increased c-kit expression in clinical PC progression. Stem cell factor expression frequency was more than 80% in all the cases. Our data suggest that the bone microenvironment up-regulates c-kit expression on PC cells, favoring their intraosseous expansion. |
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