Laminin-5 beta3A expression in LNCaP human prostate carcinoma cells increases cell migration and tumorigenicity

Interactions between extracellular matrix proteins and prostate carcinoma cells change dramatically during prostate tumor progression. We have concentrated on two key modifications that occur in the hemidesmosome in prostate carcinoma: loss of laminin-5 protein expression and altered basal cell pola...

Full description

Saved in:
Bibliographic Details
Published in:Neoplasia (New York, N.Y.) N.Y.), 2004-09, Vol.6 (5), p.468-479
Main Authors: Calaluce, Robert, Bearss, David J, Barrera, Jean, Zhao, Yu, Han, Haiyong, Beck, Shaleen K, McDaniel, Kathy, Nagle, Ray B
Format: Article
Language:English
Subjects:
Animals
Biological Assay
Carcinoma - metabolism
Carcinoma - pathology
Carcinoma - physiopathology
Cell Adhesion - genetics
Cell Adhesion Molecules - analysis
Cell Adhesion Molecules - biosynthesis
Cell Adhesion Molecules - genetics
Cell Line, Tumor
Cell Membrane - chemistry
Cell Movement
Gene Expression Profiling
Humans
Integrin alpha6 - analysis
Integrin alpha6 - metabolism
Kalinin
Male
Mice
Mice, SCID
Oligonucleotide Array Sequence Analysis
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Prostatic Neoplasms - physiopathology
Protein Isoforms - analysis
Protein Isoforms - biosynthesis
Protein Isoforms - genetics
Signal Transduction - genetics
Transfection
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Interactions between extracellular matrix proteins and prostate carcinoma cells change dramatically during prostate tumor progression. We have concentrated on two key modifications that occur in the hemidesmosome in prostate carcinoma: loss of laminin-5 protein expression and altered basal cell polarity of the alpha6beta4 integrin. We previously demonstrated two cell line-specific isoforms (beta3A and beta3B) of the LAMB3 message. Cells expressing only the beta3B isoform did not translate the beta3 protein and were unable to assemble the laminin-5 trimer. One such cell line, LNCaP, was selected to determine whether restoration of the laminin-5 beta3A isoform would cause expression of a functional laminin-5 beta3 chain, assembly and secretion of the laminin-5 trimer, and reversion to a non-neoplastic phenotype. Laminin-5 beta3A cDNA was cloned and stably transfected into LNCaP cells. We observed the restoration of the beta3 protein, but a laminin-5 trimer was not secreted. Moreover, increased cell migration was demonstrated, and tumorigenicity was increased in SCID mice. A microarray analysis, performed between transfected and nontransfected LNCaP cells, showed most changing genes to be associated with signal transduction. The beta3 chain of laminin-5 may thus play an important role in signal transduction, which may enhance cell motility and tumorigenesis.
ISSN:1522-8002