Activated leukocyte cell-adhesion molecule (ALCAM) promotes malignant phenotypes of malignant mesothelioma.
BACKGROUND
Cell-adhesion molecules play important roles involving the malignant phenotypes of human cancer cells. However, detailed characteristics of aberrant expression status of cell-adhesion molecules in malignant mesothelioma (MM) cells and their possible biological roles for MM malignancy remain poorly understood.


METHODS
DNA microarray analysis was employed to identify aberrantly expressing genes using 20 MM cell lines. Activated leukocyte cell-adhesion molecule (ALCAM) expression in MM cell lines was analyzed with quantitative reverse transcription-polymerase chain reaction and Western blot analyses in 47 primary MM specimens with immunohistochemistry. ALCAM knockdown in MM cell lines was performed with lentivirus-mediated short hairpin RNA (shRNA) transduction. Purified soluble ALCAM (sALCAM) protein was used for in vitro experiments, whereas MM cell lines infected with the sALCAM-expressing lentivirus were tested for tumorigenicity in vivo.


RESULTS
ALCAM, a member of the immunoglobulin superfamily, was detected as one of the most highly upregulated genes among 103 cell-adhesion molecules with microarray analysis. Elevated expression levels of ALCAM messenger RNA and protein were detected in all 20 cell lines. Positive staining of ALCAM was detected in 26 of 47 MM specimens (55%) with immunohistochemistry. ALCAM knockdown with shRNA suppressed cell migration and invasion of MM cell lines. Purified sALCAM protein impaired the migration and invasion of MM cells in vitro, and the infection of sALCAM-expressing virus into MM cells significantly prolonged survival periods of MM-transplanted nude mice in vivo.


CONCLUSIONS
Our study suggests that overexpression of ALCAM contributes to tumor progression in MM and that ALCAM might be a potential therapeutic target of MM.
Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Futoshi
F
Ishiguro
Hideki
H
Murakami
Tetsuya
T
Mizuno
Makiko
M
Fujii
Yutaka
Y
Kondo
Noriyasu
N
Usami
Kohei
K
Yokoi
Hirotaka
H
Osada
Yoshitaka
Y
Sekido
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010997:Pleural Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020410:Activated-Leukocyte Cell Adhesion Molecule; D014408:Biomarkers, Tumor; D012333:RNA, Messenger