Osteopontin enhances the cell proliferation induced by the epidermal growth factor in human prostate cancer cells.
BACKGROUND
Susceptibility to extracellular matrix and growth factors has been demonstrated to play a critical role in the development of prostate cancer (PCa) metastases. The aim of this study was to elucidate some mechanisms by which stroma controls tumor progression.


METHODS
In our study we tested the growth ability of the LNCaP human prostatic cell line in steroid-free culture conditions in response to osteopontin (OPN), a non-collageneous matrix protein, localized in large amounts in the bone.


RESULTS
In the LNCaP cell model, OPN stimulates cell proliferation in serum-free medium and colony growth at high dilution but this effect is visible only in presence of epidermal growth factor (EGF). Proliferation induced by OPN is accompanied by a sustained activation of EGF receptor (EGFR) whose phosphorylation is detectable up to 12 hr after treatment in association with EGF. The colocalization of integrin beta1, a ligand of OPN, and of EGFR on the cellular membrane, suggests that the association of these cell surface receptors may be the principal mechanism involved in the long-term activation of the EGFR.


CONCLUSIONS
Our data describe a new possible mechanism involved in the establishment of bone metastases which may also account for the formation of androgen-independent cellular clones, frequently responsible of the clinical progression of PCa.
Angelucci
Adriano
A
Department of Experimental Medicine, University of L'Aquila, Medical School, Coppito-2, L'Aquila, Italy. festucci@univaq.it
Festuccia
Claudio
C
Gravina
Giovanni Luca
GL
Muzi
Paola
P
Bonghi
Loriana
L
Vicentini
Carlo
C
Bologna
Mauro
M
D001859:Bone Neoplasms / Q000503:physiopathology* / Q000556:secondary*; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects*; D016207:Cytokines; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D008297:Male; D053495:Osteopontin; D010750:Phosphoproteins; D011471:Prostatic Neoplasms / Q000473:pathology*; D012795:Sialoglycoproteins / Q000494:pharmacology*; D017154:Stromal Cells / Q000502:physiology*
D016207:Cytokines; D010750:Phosphoproteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors