Promatrilysin expression is induced by fibroblast growth factors in the prostatic carcinoma cell line LNCaP but not in normal primary prostate epithelial cells.
BACKGROUND
It has been determined that prostate cancer cells overexpress the matrix metalloprotease matrilysin (MMP-7), but the factors regulating this expression have not been identified. Fibroblast growth factors (FGF), which are expressed in the prostate, might participate in paracrine regulation of matrilysin expression by prostate cancer cells.


METHODS
We tested the ability of recombinant FGF proteins and prostate fibroblast-conditioned media (PFCM) to induce promatrilysin expression in the prostate carcinoma cell line, LNCaP, and in normal prostate epithelial (PrEC) cells. We also characterized prostate fibroblast FGF expression by reverse transcriptase-polymerase chain reaction (RT-PCR). An inhibitor of FGF receptor activation (SU5402) was used to determine the role of FGF proteins in the induction of promatrilysin expression by PFCM.


RESULTS
Recombinant FGF-1, FGF-2, FGF-9, FGF-10, and PFCM significantly induced promatrilysin expression in LNCaP cells but not in PrEC cells. Prostate fibroblasts express mRNAs for these FGF proteins, and inhibition of LNCaP cell FGF receptors with SU5402 substantially reduced the induction of promatrilysin expression by PFCM.


CONCLUSIONS
Stromally expressed FGF proteins induce promatrilysin expression in a prostate carcinoma cell, and may provide a mechanism for the overexpression of promatrilysin observed in prostate cancer.
Klein
R D
RD
Department of Radiation Oncology, University of Arizona Health Sciences Center, Tucson, Arizona 85724-5024, USA.
Maliner-Jongewaard
M S
MS
Udayakumar
T S
TS
Boyd
J L
JL
Nagle
R B
RB
Bowden
G T
GT
D002277:Carcinoma / Q000201:enzymology*; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D011467:Prostate / Q000187:drug effects / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D008666:Metalloendopeptidases; C099583:promatrilysin