C-kit and its ligand stem cell factor: potential contribution to prostate cancer bone metastasis.
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.
Wiesner
Christoph
C
Department of Urology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Nabha
Sanaa M
SM
Dos Santos
Emanuel Burck
EB
Yamamoto
Hamilto
H
Meng
Hong
H
Melchior
Sebastian W
SW
Bittinger
Fernando
F
Thüroff
Joachim W
JW
Vessella
Robert L
RL
Cher
Michael L
ML
Bonfil
R Daniel
RD
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary; D018929:Cell Culture Techniques; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000378:metabolism*; D015854:Up-Regulation
D008024:Ligands; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit