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Activated leukocyte cell adhesion molecule expression correlates with the WNT subgroup in medulloblastoma and is involved in regulating tumor cell proliferation and invasion.
- Source :
-
PloS one [PLoS One] 2020 Dec 03; Vol. 15 (12), pp. e0243272. Date of Electronic Publication: 2020 Dec 03 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Cluster of differentiation (CD) 166 or activated leukocyte cell adhesion molecule (ALCAM) is a transmembrane molecule known to be an intercellular adhesion factor. The expression and function of ALCAM in medulloblastoma (MB), a pediatric brain tumor with highly advanced molecular genetics, remains unclear. Therefore, this study aimed to clarify the significance and functional role of ALCAM expression in MB. ALCAM expression in 45 patients with MB was evaluated by immunohistochemical analysis of formalin-fixed paraffin-embedded clinical specimens and the relationship between ALCAM expression and pathological type/molecular subgroup, such as WNT, SHH, Group 3, and Group 4, was examined. Eight ALCAM positive (18%), seven partially positive (16%), and 30 negative (67%) cases were detected. All seven cases of the WNT molecular subgroup were ALCAM positive and ALCAM expression strongly correlated with this subgroup (P < 0.0001). In addition, functional studies using MB cell lines revealed ALCAM expression affected proliferation and migration as a positive regulator in vitro. However, ALCAM silencing did not affect survival or the formation of leptomeningeal dissemination in an orthotopic mouse model, but did induce a malignant phenotype with increased tumor cell invasion at the dissemination sites (P = 0.0029). In conclusion, our results revealed that ALCAM exhibited highly specific expression in the WNT subgroup of MB. Furthermore, we demonstrated that the cell kinetics of MB cell lines can be altered by the expression of ALCAM.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Activated-Leukocyte Cell Adhesion Molecule genetics
Adolescent
Animals
Antigens, CD physiology
Biomarkers, Tumor metabolism
Brain Neoplasms genetics
Cell Adhesion genetics
Cell Adhesion Molecules, Neuronal physiology
Cell Movement genetics
Cell Proliferation genetics
Cerebellar Neoplasms genetics
Child
Child, Preschool
Female
Fetal Proteins physiology
Gene Expression genetics
Gene Expression Profiling
Humans
Infant
Japan epidemiology
Male
Medulloblastoma physiopathology
Mice
Neoplasm Invasiveness
RNA, Messenger genetics
Wnt Proteins genetics
Young Adult
Antigens, CD metabolism
Cell Adhesion Molecules, Neuronal metabolism
Fetal Proteins metabolism
Medulloblastoma metabolism
Wnt Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 15
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 33270750
- Full Text :
- https://doi.org/10.1371/journal.pone.0243272