C-Kit and its ligand stem cell factor (SCF): Potential contribution to prostate cancer bone metastasis

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 Cher and R Daniel Bonfil

Year 2008, Volume 10, Issue 9

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 (BMS) cells express a membrane-bound SCF isoform and release a soluble SCF at different levels. BMS cells revealed strong expression of c-kit, while 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. SCF expression frequency was over 80 % in all the cases. Our data suggest that the bone microenvironment upregulates c-kit expression on PC cells, favoring their intraosseous expansion.

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