Paracrine calcitonin in prostate cancer is linked to CD44 variant expression and invasion.
Anticancer Res
; 25(3B): 2075-83, 2005.
Article
em En
| MEDLINE
| ID: mdl-16158948
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 ANDMETHODS:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Calcitonina
/
Receptores de Hialuronatos
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos