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PMID: 15548355 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Neoplasia (New York, N.Y.) ·Vol. 6 ·No. 5 ·2004-00-00 ·Pages 468-79

Calaluce R, Bearss DJ, Barrera J, Zhao Y, Han H, Beck SK, McDaniel K, Nagle RB

Abstract

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.

MeSH Terms
Animals Biological Assay Carcinoma/metabolism,pathology,physiopathology Cell Adhesion/genetics Cell Adhesion Molecules/analysis,biosynthesis,genetics Cell Line, Tumor Cell Membrane/chemistry Cell Movement Gene Expression Profiling Humans Integrin alpha6/analysis,metabolism Male Mice Mice, SCID Oligonucleotide Array Sequence Analysis Prostatic Neoplasms/metabolism,pathology,physiopathology Protein Isoforms/analysis,biosynthesis,genetics Signal Transduction/genetics Transfection
Chemicals
Cell Adhesion Molecules Integrin alpha6 Protein Isoforms kalinin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Calaluce Robert
Arizona Cancer Center, University of Arizona Health Sciences Center, Tucson, AZ, USA. rcalaluce@azcc.arizona.edu
Bearss David J
Barrera Jean
Zhao Yu
Han Haiyong
Beck Shaleen K
McDaniel Kathy
Nagle Ray B
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Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1522-8002
DOI
10.1593/neo.03499
Email
rcalaluce@azcc.arizona.edu
Published
2004-00-00
Pages
468-79
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1531651
Subset
IM
Grants
NCI NIH HHS · P30 CA023074 · United States
NCI NIH HHS · 2P30 CA023074-26 · United States
NCI NIH HHS · K08 CA090662 · United States
NCI NIH HHS · P01 CA056666 · United States
NCI NIH HHS · K08 CA90662-01 · United States
NCI NIH HHS · 5 P01 CA56666-05 · United States
External Links
PubMed source DOI: 10.1593/neo.03499 PMC Full Text
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