HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) All Versions of this Article: ERC-08-0136v1 15/4/953    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shah, G. Articles by Chaudhary, J. Search for Related Content PubMed PubMed Citation Articles by Shah, G. Articles by Chaudhary, J.

G Shah, Pharmacology, University of Louisiana, Monroe, 71209, United States
S Thomas, Pharmacology, University of Louisiana, Monroe, United States
A Muralidharan, Pharmacology, University of Louisiana, Monroe, United States
Y Liu, Medicine, University of Arkansas for Medical Sciences, Little Rock, United States
P Hermonat, Medicine, University of Arkansas for Medical Sciences, Little Rock, United States
J Williams, Urology, Louisiana State University Health Sciences Center, Shreveport, United States
J Chaudhary, Biological Sciences, Clark Atlanta University, Atlanta, United States

Correspondence: Girish Shah, Email: shah{at}ulm.edu

Abstract

Expression of calcitonin (CT) and its receptor (CTR) is elevated in advanced prostate cancer (PC). Although the significance of CT-CTR axis in PC cell growth, invasion, and epithelial to mesenchymal transition has been established, its role in tumor metastasis has not been examined. To examine the role of CT-CTR axis in tumor metastasis, we employed stable CT-CTR activated and silenced system of three PC cell lines, LNCaP cells that lack endogenous CT, PC-3 cells that lack endogenous CTR, and PC-3M cells that co-express CT and CTR. Enforced expression of CT in LNCaP cells and CTR in PC-3 cells increased their ability to form orthotopic tumors and distant metastases in multiple organs. In contrast, silencing of CT expression in PC-3M cells not only reduced their tumorigenicity, but completely abrogated their metastatic potential. To investigate the effect of in vivo silencing of CT expression on tumor growth, we employed recombinant adeno-associated virus (rAAV) to deliver anti-CT ribozymes in preexisting tumors of nude mice and LPB-Tag transgenic mice. rAAV-CT- treatment not only abrogated the growth of pre-implanted tumors in nude mice, but also significantly reduced the growth of spontaneous tumors in LPB-Tag mice. Analysis of CT upregulated and silenced PC-3M transcriptomes revealed 105 genes affected by the modulation of CT expression. These CT signature genes generated survival, adhesion, pro-inflammatory and pro-metastatic pathways. Added together, these data indicate a pivotal role for CT-CTR axis in prostate cancer metastasis, and may serve as a potential therapeutic target for advanced PC.