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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.

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.

SUBMITTER: Achiha T

PROVIDER: S-EPMC7714159 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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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.

Achiha Takamune T Kijima Noriyuki N Kodama Yoshinori Y Kagawa Naoki N Kinoshita Manabu M Fujimoto Yasunori Y Nonaka Masahiro M Fukai Junya J Inoue Akihiro A Nishida Namiko N Yamanaka Takumi T Harada Atsuko A Mori Kanji K Tsuyuguchi Naohiro N Uda Takehiro T Ishibashi Kenichi K Tomogane Yusuke Y Sakamoto Daisuke D Shofuda Tomoko T Yoshioka Ema E Kanematsu Daisuke D Mano Masayuki M Luu Betty B Taylor Michael D MD Kanemura Yonehiro Y Kishima Haruhiko H

PloS one 20201203 12

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 ...[more]

PMID: 33270750

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Project description:Multiple sclerosis is a chronic neuroinflammatory disorder characterized by demyelination, oligodendrocyte damage/loss and neuroaxonal injury in the context of immune cell infiltration in the central nervous system. No neuroprotective therapy is available to promote the survival of oligodendrocytes and protect their myelin processes in immune-mediated demyelinating diseases. Pro-inflammatory CD4 T helper (Th)17 cells can directly interact with oligodendrocytes in multiple sclerosis and its animal model, causing injury to myelinating processes and cell death through direct contact. However, the molecular mechanisms underlying the close contact and subsequent detrimental interaction of Th17 cells with oligodendrocytes remain unclear. In this study we conducted single cell RNA sequencing of human primary oligodendrocytes cultured alone, in contact or separated by an insert with primary Th17 polarized T cells and identified several cell adhesion molecules that may modulate T cell contact mediated damage of oligodendrocytes. Furthermore, we used flow cytometry and immunofluorescence studies on central nervous system tissue from multiple sclerosis subjects, its animal model and controls to characterize the expression of cell adhesion molecules by mature oligodendrocytes. We found that a significant proportion of human and murine mature oligodendrocytes express melanoma cell adhesion molecule and activated leukocyte cell adhesion molecule in multiple sclerosis, EAE and controls although their regulation differ between human and mouse. We observed that exposure to pro-inflammatory cytokines or to human activated T cells are associated with a marked downregulation of the expression of melanoma cell adhesion molecule but not activated leukocyte cell adhesion molecule at the surface of human primary oligodendrocytes. Furthermore, we used in vitro live-imaging, immunofluorescence, and flow cytometry to determine the contribution of these molecules to Th17-polarized cell adhesion and cytotoxicity towards human oligodendrocytes. Silencing and blocking activated leukocyte cell adhesion molecule but not melanoma cell adhesion molecule limited prolonged interactions between oligodendrocytes and Th17-polarized cells, resulting in decreased adhesion of Th17-polarized cells to oligodendrocytes and conferred significant protection of oligodendrocytic processes.

Dataset Information

Activated leukocyte cell adhesion molecule expression correlates with the WNT subgroup in medulloblastoma and is involved in regulating tumor cell proliferation and invasion.

Publications

Activated leukocyte cell adhesion molecule expression correlates with the WNT subgroup in medulloblastoma and is involved in regulating tumor cell proliferation and invasion.

Similar Datasets

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