| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Departments of Surgery,
2 Experimental Medicine and
3 Basic and Applied Biology, University of L’Aquila via Vetoio, Coppito 2, 67100 L’Aquila, Italy
(Requests for offprints should be addressed to A Angelucci; Email: adriano.angelucci{at}gmail.com)
The activation of epidermal growth factor receptor (EGF-R) plays a key role in the promotion of proliferation and invasion in prostatic carcinoma (PCa). Gefitinib (Iressa; ZD1839), an orally active EGF-R tyrosine kinase inhibitor, has shown an important anti-proliferative activity in tumors expressing EGF-R both in vitro and in vivo. Our aim was to elucidate the role of gefitinib in the modulation of the metastatic spread of PCa cells. The therapeutic role of gefitinib was investigated by evaluating the proliferative and invasive ability of the PCa cell line PC3 and of its high metastatic sub-line, PCb2, by in vitro assays and intracardiac injection in nude mice. The inhibitory effect of gefitinib was tested in vivo by injecting PCa cells subcutaneously or in the left ventricle of nude mice and by administrating daily 150 mg/kg of gefitinib. While xenograft growth was equally reduced in all PCa lines (about 50%), the bone metastasis formation was inhibited especially for the high metastatic PCb2 sub-line (81%) in comparison to PC3 cells (47%). The comparative in vitro analysis among PCa cell lines showed that PCb2 cells were more sensitive to the inhibitory effect of gefitinib in their invasive ability compared to parental PC3 cells but not in their proliferation rate. Moreover, PCb2 cells demonstrated an increased invasive ability in vitro in response to bone stromal cell conditioned medium (BCM). The simultaneous presence of 0.1 ng/ml gefitinib was sufficient to reduce the number of invaded cells in the presence of both EGF and BCM. The molecular characterization of the highly aggressive PCa sub-lines demonstrated that this phenomenon was associated with an increment in uPA/uPAR axis but not in EGF-R expression. In conclusion, our data suggest that the use of gefitinib as a therapeutic agent may be indicated in the control of PCa spreading to bone.
This article has been cited by other articles:
|
|
 |
|
  A. L. Teixeira, R. Ribeiro, D. Cardoso, D. Pinto, F. Lobo, A. Fraga, F. Pina, F. Calais-da-Silva, and R. Medeiros Genetic Polymorphism in EGF Is Associated with Prostate Cancer Aggressiveness and Progression-Free Interval in Androgen Blockade-Treated Patients Clin. Cancer Res., June 1, 2008; 14(11): 3367 - 3371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mimeault, P. P. Mehta, R. Hauke, and S. K. Batra Functions of Normal and Malignant Prostatic Stem/Progenitor Cells in Tissue Regeneration and Cancer Progression and Novel Targeting Therapies Endocr. Rev., April 1, 2008; 29(2): 234 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Angelucci, S. Garofalo, S. Speca, A. Bovadilla, G. L. Gravina, P. Muzi, C. Vicentini, and M. Bologna Arachidonic acid modulates the crosstalk between prostate carcinoma and bone stromal cells Endocr. Relat. Cancer, March 1, 2008; 15(1): 91 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhu, X. Jia, G. Xiao, Y. Kang, N. C. Partridge, and L. Qin IMPLICATIONS FOR OSTEOLYTIC BONE METASTASES J. Biol. Chem., September 14, 2007; 282(37): 26656 - 26664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mimeault, S. L. Johansson, G. Vankatraman, E. Moore, J.-P. Henichart, P. Depreux, M.-F. Lin, and S. K. Batra Combined targeting of epidermal growth factor receptor and hedgehog signaling by gefitinib and cyclopamine cooperatively improves the cytotoxic effects of docetaxel on metastatic prostate cancer cells Mol. Cancer Ther., March 1, 2007; 6(3): 967 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Normanno and W. J Gullick Epidermal growth factor receptor tyrosine kinase inhibitors and bone metastases: different mechanisms of action for a novel therapeutic application? Endocr. Relat. Cancer, March 1, 2006; 13(1): 3 - 6. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
