Cloning and characterization of hepaCAM, a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma

Moh, Mei Chung; Lee, Lay Hoon; Shen, Shoucang

doi:10.1016/j.jhep.2005.01.025

Cited by 65 publications

(45 citation statements)

References 29 publications

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“…The protein is composed of an extracellular region containing two Ig-like domains, one V-set and one C2 domain; a transmembrane region and a low complexity, proline-rich intracellular region (Moh et al, 2005). The structure of Glial-CAM is similar to several members of the CTX (cortical thymocyte marker in Xenopus) gene family of adhesion molecules such as JAM and ESAM (Chung et al, 2005).…”

Section: Glialcam Structure and Sequencementioning

confidence: 99%

“…The corresponding cDNA was cloned by exon assembly using a human brain genomic DNA library and was found to be identical to hepatocyte cell adhesion molecule (hepaCAM) (Chung et al, 2005). HepaCAM, located on human chromosome 11q24, is an IgCAM that was originally identified as a putative tumor suppressor gene in human liver.…”

Section: Introductionmentioning

confidence: 99%

“…Through cell spreading, detachment, and wound healing assays it has been demonstrated that hepaCAM is a cell adhesion molecule involved in cell-matrix interactions (Moh et al, 2005). hepaCAM has also been suggested as a tumor suppressor gene, as it is strongly downregulated in hepatocellular carcinoma and shows antiproliferative properties in vitro (Chung et al, 2005). Recently, hepaCAM was identified in cDNA libraries obtained from dibutyryl cAMP stimulated primary rat Schwann cells and in newborn rat sciatic nerves, suggesting a potential role for hepaCAM in the NS and particularly, at early stages of axon-glia interactions and/or in myelination (Spiegel et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

Favre-Kontula

Rolland

Bernasconi

et al. 2008

Glia

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Using structure based genome mining targeting vascular endothelial and platelet derived growth factor immunoglobulin (Ig) like folds, we have identified a sequence corresponding to a single transmembrane protein with two Ig domains, which we cloned from a human brain cDNA library. The cDNA is identical to hepatocyte cell adhesion molecule (hepaCAM), which was originally described as a tumor suppressor gene in liver. Here, we show that the protein is predominantly expressed in the mouse and human nervous system. In liver, the expression is very low in humans, and is not detected in mice. To identify the central nervous system (CNS) regions and cell types expressing the protein, we performed a LacZ reporter gene assay on heterozygous mice in which one copy of the gene encoding the novel protein had been replaced with beta-galactosidase. beta-galactosidase expression was prominent in white matter tracts of the CNS. Furthermore, expression was detected in ependymal cells of the brain ventricular zones and the central canal of the spinal cord. Double labeling experiments showed expression mainly in CNPase positive oligodendrocytes (OL). Since the protein is predominantly expressed in the CNS glial cells, we named the molecule glial cell adhesion molecule (GlialCAM). A potential role for GlialCAM in myelination was supported by its up-regulation during postnatal mouse brain development, where it was concomitantly expressed with myelin basic protein (MBP). In addition, in vitro, GlialCAM was observed in various developmental stages of OL and in astrocytes in processes and at cell contact sites. In A2B5 positive OL, GlialCAM colocalizes with GAP43 in OL growth cone like structures. Overall, the data presented here indicate a potential function for GlialCAM in glial cell biology.

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Section: Glialcam Structure and Sequencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

Favre-Kontula

Rolland

Bernasconi

et al. 2008

Glia

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“…HepaCAM was first identified in 2005 as a cell adhesion molecule belonging to the immunoglobulin superfamily in [3]. The expression of hepaCAM gene is frequently lost in various human cancer cells and tissues [3,4].…”

Section: Renal Tumor-derived Exosomes Inhibit Hepacam Expression Of Rmentioning

confidence: 99%

“…The expression of hepaCAM gene is frequently lost in various human cancer cells and tissues [3,4]. The re-expression of hepaCAM in RCC and breast cancer cells inhibits cell proliferation [5]; as a result, cell cycle arrest occurs at the G2/M phase [4].…”

Section: Renal Tumor-derived Exosomes Inhibit Hepacam Expression Of Rmentioning

confidence: 99%

Renal tumor-derived exosomes inhibit hepaCAM expression of renal carcinoma cells in a p-AKT-dependent manner

Jiang¹,

Zhang²,

Tan³

et al. 2014

neo

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HepaCAM mediates cancer cell proliferation, migration and differentiation. Our previous studies showed the effects of hepaCAM on the inhibition of renal carcinoma cell proliferation. To further investigate the reason for the low expression of hepaCAM in renal carcinoma and the corresponding molecular mechanisms, we detected renal carcinoma OS-RC-2 cell lines containing high expression of hepaCAM; and hepaCAM and p-AKT were also detected in these cells. Exosomes were isolated and purified from the supernatant liquid of OS-RC-2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry analysis were conducted to determine the effect of exosomes on the proliferation and cycle distribution of OS-RC-2 cells. OS-RC-2 cells (high expression of hepaCAM) were treated with exosomes or plus MK-2206 (AKT inhibitor); and hepaCAM, AKT and p-AKT were detected in these cells by western blot analysis. The correlation between hepaCAM and p-AKT was analysed by immunohistochemical method. Results showed that hepaCAM re-expression in OS-RC-2 cell lines resulted in significant weakening of proliferation ability and more prominent G0/G1 population as well as reduction of p-AKT protein. The increase in proliferation caused by exosomes was followed by hepaCAM downregulation and p-AKT upregulation in OS-RC-2 cells (high expression of hepaCAM). By comparison, the promotion of proliferation caused by exosomes was weakened and hepaCAM expression changed after MK-2206 treatment; however, this change was not significant. HepaCAM was negatively correlated with p-AKT protein in renal cell carcinoma tissues. Therefore, renal tumor-derived exosomes may be an important factor resulting in the low expression of hepaCAM by upregulating p-AKT in renal carcinoma.

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Astrocytes in the regulation of cerebrovascular functions

Cohen-Salmon

Slaoui

Mazaré

et al. 2020

Glia

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Astrocytes are the most numerous type of neuroglia in the brain and have a predominant influence on the cerebrovascular system; they control perivascular homeostasis, the integrity of the blood–brain barrier, the dialogue with the peripheral immune system, the transfer of metabolites from the blood, and blood vessel contractility in response to neuronal activity. These regulatory processes occur in a specialized interface composed of perivascular astrocyte extensions that almost completely cover the cerebral blood vessels. Scientists have only recently started to study how this interface is formed and how it influences cerebrovascular functions. Here, we review the literature on the astrocytes' role in the regulation of the cerebrovascular system. We cover the anatomy and development of the gliovascular interface, the known gliovascular functions, and molecular factors, the latter's implication in certain pathophysiological situations, and recent cutting‐edge experimental tools developed to examine the astrocytes' role at the vascular interface. Finally, we highlight some open questions in this field of research.

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Cloning and characterization of hepaCAM, a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma

Cited by 65 publications

References 29 publications

GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

Renal tumor-derived exosomes inhibit hepaCAM expression of renal carcinoma cells in a p-AKT-dependent manner

Astrocytes in the regulation of cerebrovascular functions

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Cloning and characterization of hepaCAM, a novel Ig-like cell adhesion molecule suppressed in human hepatocellular carcinoma

Cited by 65 publications

References 29 publications

GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

Renal tumor-derived exosomes inhibit hepaCAM expression of renal carcinoma cells in a p-AKT-dependent manner

Astrocytes in the regulation of cerebrovascular functions

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Product

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Renal tumor-derived exosomes inhibit hepaCAM expression of renal carcinoma cells in a p-AKT-dependent manner