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 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.
Calaluce
Robert
R
Arizona Cancer Center, University of Arizona Health Sciences Center, Tucson, AZ, USA. rcalaluce@azcc.arizona.edu
Bearss
David J
DJ
Barrera
Jean
J
Zhao
Yu
Y
Han
Haiyong
H
Beck
Shaleen K
SK
McDaniel
Kathy
K
Nagle
Ray B
RB
D000818:Animals; D001681:Biological Assay; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement; D020869:Gene Expression Profiling; D006801:Humans; D039503:Integrin alpha6 / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D039503:Integrin alpha6; D020033:Protein Isoforms; D000097794:Kalinin