Faculty Collaboration Database

Paracrine calcitonin in prostate cancer is linked to CD44 variant expression and invasion. Anticancer Res 2005;25(3B):2075-83

Date

09/15/2005

Pubmed ID

16158948

Scopus ID

2-s2.0-21344456362 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

BACKGROUND: Calcitonin (CT) exerts an autocrine/paracrine influence on prostatic tumor invasion through coupling to transduction protein Gsalpha. Cell adhesion glycoprotein CD44 variant v7-v10 also faciliates invasion, but its modulation by the CT-Gsalpha system was unexplored.

MATERIALS AND METHODS: LnCaP, PC-3 and metastasis-derived PC-3M cell lines were studied, including cells modified therefrom: Gsalpha-QL, expressing mutant constitutively active Gsalpha protein, and CT+, overexpressing CT. CD44 variant expression was evaluated in vivo after orthotopic implantion into nude mice, and in vitro by real-time RT-PCR and Western blotting.

RESULTS: Both mRNA and protein levels of the CD44 variant were minimal in PC-3M tumor implants, but elevated in Gsalpha-QL. Exogenous CT stimulated invasion into Matrigel strongly in LnCaP and CT+, and less in PC-3 and Gsalpha-QL. By Western blot analysis, untreated Gsalpha-QL and CT+ cells overexpressed CD44 variant compared with LnCaP or PC-3. By quantitative RT-PCR, exogenous CT dose-dependently increased CD44 variant mRNA to seven-fold. Pharmacologic agents that stimulated or inhibited Gsalpha activity or stimulated adenylyl cyclase produced proportionate dose-dependent effects on both CD44 variant expression and Matrigel invasion.

CONCLUSION: This paracrine factor, acting though cyclic AMP, regulates the expression of CD44v7-10, which modulates the tumor phenotype.

Author List

Iczkowski KA, Omara-Opyene AL, Kulkarni TR, Pansara M, Shah GV

MESH terms used to index this publication - Major topics in bold

Adenylyl Cyclases
Animals
Calcitonin
Cell Line, Tumor
Dose-Response Relationship, Drug
GTP-Binding Protein alpha Subunits, Gs
Guanylyl Imidodiphosphate
Humans
Hyaluronan Receptors
In Situ Hybridization
Male
Mice
Mice, Nude
Neoplasm Invasiveness
Prostatic Neoplasms
Protein Isoforms
RNA, Messenger